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Shi H, Zhao XH, Peng Q, Zhou XL, Liu SS, Sun CC, Cao QY, Zhu SP, Sun SY. Green tea polyphenols alleviate di (2-ethylhexyl) phthalate-induced testicular injury in mice via lncRNA-miRNA-mRNA axis†. Biol Reprod 2025; 112:485-500. [PMID: 39658192 DOI: 10.1093/biolre/ioae179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 11/17/2024] [Accepted: 12/07/2024] [Indexed: 12/12/2024] Open
Abstract
Di(2-ethylhexyl) phthalate (DEHP) is a commonly used plasticizer known for its toxic effects on the male reproductive system. Green tea polyphenols (GTPs), recognized for their antioxidant and anti-inflammatory properties, have demonstrated protective effects on various organs, but the mechanisms by which GTPs mitigate DEHP-induced testicular damage remain unclear. Healthy male C57BL/6J mice were divided into five groups: control, DEHP, DEHP + GTP treatment, GTP, and oil groups. Testicular histopathological changes were assessed using hematoxylin-eosin (H&E), periodic acid-Schiff (PAS), and Masson staining. Ultrastructural alterations were examined through transmission electron microscopy. High-throughput sequencing was performed to analyze the expression of mRNA, miRNA, and lncRNA and construct an lncRNA-miRNA-mRNA regulatory network for identifying key regulatory axes. Mice in the DEHP group exhibited significant testicular damage, including reduced sperm count, mitochondrial deformation, and endoplasmic reticulum dilation. GTP treatment notably improved testicular structural integrity, restored sperm count, and alleviated mitochondrial and endoplasmic reticulum damage. Additionally, DEHP significantly increased activated CD8+ T cells, which were reduced with GTP treatment. High-throughput sequencing revealed that GTP treatment exerted protective effects through the regulation of six key lncRNA-miRNA-mRNA axes. GTPs significantly protect against DEHP-induced testicular damage, and the lncRNA-miRNA-mRNA regulatory axes play a potential role in this process.
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Affiliation(s)
- Heng Shi
- Department of Traditional Chinese Medicine, The First Affiliated Hospital of Jinan University, No. 613 West Huangpu Ave, Guangzhou 510630, China
- Department of Gastroenterology, The Central Hospital of Shaoyang, No. 360, Baoqing Middle Road, Hongqi Street, Daxiang District, Shaoyang 42200, China
| | - Xin-Hai Zhao
- Department of Traditional Chinese Medicine, The First Affiliated Hospital of Jinan University, No. 613 West Huangpu Ave, Guangzhou 510630, China
| | - Qin Peng
- Department of Gastroenterology, The Central Hospital of Shaoyang, No. 360, Baoqing Middle Road, Hongqi Street, Daxiang District, Shaoyang 42200, China
| | - Xian-Ling Zhou
- Department of Traditional Chinese Medicine, The First Affiliated Hospital of Jinan University, No. 613 West Huangpu Ave, Guangzhou 510630, China
| | - Si-Si Liu
- Department of Pathology, The Central Hospital of Shaoyang, No. 360, Baoqing Middle Road, Hongqi Street, Daxiang District, Shaoyang 42200, China
| | - Chuan-Chuan Sun
- Department of Traditional Chinese Medicine, The First Affiliated Hospital of Jinan University, No. 613 West Huangpu Ave, Guangzhou 510630, China
| | - Qiu-Yu Cao
- Department of Gynecologic, Jiangmen Hospital Affiliated to Jinan University, No. 30, Huayuan East Road, Jiangmen 529000, China
| | - Shi-Ping Zhu
- Department of Traditional Chinese Medicine, The First Affiliated Hospital of Jinan University, No. 613 West Huangpu Ave, Guangzhou 510630, China
| | - Sheng-Yun Sun
- Department of Traditional Chinese Medicine, The First Affiliated Hospital of Jinan University, No. 613 West Huangpu Ave, Guangzhou 510630, China
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Markowska A, Antoszczak M, Markowska J, Huczyński A. Role of Epigallocatechin Gallate in Selected Malignant Neoplasms in Women. Nutrients 2025; 17:212. [PMID: 39861342 PMCID: PMC11767294 DOI: 10.3390/nu17020212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Revised: 01/04/2025] [Accepted: 01/07/2025] [Indexed: 01/27/2025] Open
Abstract
Tea is a significant source of flavonoids in the diet. Due to different production processes, the amount of bioactive compounds in unfermented (green) and (semi-)fermented tea differs. Importantly, green tea has a similar composition of phenolic compounds to fresh, unprocessed tea leaves. It consists primarily of monomeric flavan-3-ols, known as catechins, of which epigallocatechin gallate (EGCG) is the most abundant. Thanks to its antioxidant, antiproliferative, and antiangiogenic properties, EGCG has attracted the scientific community's attention to its potential use in preventing and/or combating cancer. In this review article, we summarize the literature reports found in the Google Scholar and PubMed databases on the anticancer effect of EGCG on selected malignant neoplasms in women, i.e., breast, cervical, endometrial, and ovarian cancers, which have been published over the last two decades. It needs to be emphasized that EGCG concentrations reported as effective against cancer cells are typically higher than those found in plasma after polyphenol administration. Moreover, the low bioavailability and absorption of EGCG appear to be the main reasons for the differences in the effects between in vitro and in vivo studies. In this context, we also decided to look at possible solutions to these problems, consisting of combining the polyphenol with other bioactive components or using nanotechnology. Despite the promising results of the studies conducted so far, mainly in vitro and on animal models, there is no doubt that further, broad-based activities are necessary to unequivocally assess the potential use of EGCG in oncological treatment to combat cancer in women.
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Affiliation(s)
- Anna Markowska
- Department of Perinatology and Women’s Health, Poznań University of Medical Sciences, 60-535 Poznań, Poland;
| | - Michał Antoszczak
- Department of Medical Chemistry, Faculty of Chemistry, Adam Mickiewicz University, 61-614 Poznań, Poland;
| | - Janina Markowska
- Gynecological Oncology Center, Poznańska 58A, 60-850 Poznań, Poland
| | - Adam Huczyński
- Department of Medical Chemistry, Faculty of Chemistry, Adam Mickiewicz University, 61-614 Poznań, Poland;
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Liu GH, Yao ZQ, Chen GQ, Li YL, Liang B. Potential Benefits of Green Tea in Prostate Cancer Prevention and Treatment: A Comprehensive Review. Chin J Integr Med 2024; 30:1045-1055. [PMID: 38561489 DOI: 10.1007/s11655-024-4100-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/23/2023] [Indexed: 04/04/2024]
Abstract
Prostate cancer is a prevalent and debilitating disease that necessitates effective prevention and treatment strategies. Green tea, a well-known beverage derived from the Camellia sinensis plant, contains bioactive compounds with potential health benefits, including catechins and polyphenols. This comprehensive review aims to explore the potential benefits of green tea in prostate cancer prevention and treatment by examining existing literature. Green tea possesses antioxidant, anti-inflammatory, and anti-carcinogenic properties attributed to its catechins, particularly epigallocatechin gallate. Epidemiological studies have reported an inverse association between green tea consumption and prostate cancer risk, with potential protection against aggressive forms of the disease. Laboratory studies demonstrate that green tea components inhibit tumor growth, induce apoptosis, and modulate signaling pathways critical to prostate cancer development and progression. Clinical trials and human studies further support the potential benefits of green tea. Green tea consumption has been found to be associated with a reduction in prostate-specific antigen levels, tumor markers, and played a potential role in slowing disease progression. However, challenges remain, including optimal dosage determination, formulation standardization, and conducting large-scale, long-term clinical trials. The review suggests future research should focus on combinatorial approaches with conventional therapies and personalized medicine strategies to identify patient subgroups most likely to benefit from green tea interventions.
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Affiliation(s)
- Gui-Hong Liu
- Department of Urology, Sanya Central Hospital (The Third People's Hospital of Hainan Province), Sanya City, Hainan Province, 572000, China
| | - Ze-Qin Yao
- Department of Urology, Sanya Central Hospital (The Third People's Hospital of Hainan Province), Sanya City, Hainan Province, 572000, China
| | - Guo-Qiang Chen
- Department of Urology, Sanya Central Hospital (The Third People's Hospital of Hainan Province), Sanya City, Hainan Province, 572000, China
| | - Ya-Lang Li
- Department of Urology, Yuzhou People's Hospital, Xuchang City, Henan Province, 461670, China
| | - Bing Liang
- Department of Urology, Sanya Central Hospital (The Third People's Hospital of Hainan Province), Sanya City, Hainan Province, 572000, China.
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4
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Liu M, Ning Z, Cheng Y, Zheng Z, Yang X, Zheng T, Li N, Wu JL. The key to 2,6-dichloro-1,4-benzoquinone reproductive toxicity and green tea detoxification: Covalent binding and competitive binding. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2024; 286:117239. [PMID: 39454356 DOI: 10.1016/j.ecoenv.2024.117239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/08/2024] [Revised: 09/24/2024] [Accepted: 10/19/2024] [Indexed: 10/28/2024]
Abstract
Halobenzoquinones (HBQs) are ubiquitous disinfection by-products (DBPs) in chlorinated drinking water with various health risks including reproductive toxicity, while the potential mechanisms are still unclear. Although green tea exhibits common detoxifying properties, its ability to mitigate the toxicity of HBQs still needs to be further deepened and explored. This study attempted to investigate the possible mechanism of the most common HBQ, 2,6-dichloro-1,4-benzoquinone (2,6-DCBQ) induced reproductive toxicity and elucidate the protective effect of green tea using a series of liquid chromatography-tandem mass spectrometry (LC-MS) approaches. Firstly, in vivo experiments showed that 2,6-DCBQ could induce testicular damage in male rats via significantly decreasing sperm-associated Leydig cells and seminiferous tubules. Then, in vitro incubation of 2,6-DCBQ with amino acids suggested that 2,6-DCBQ could bind to proteins via residues of cysteine or lysine and provided five additional modification patterns. Following, proteomics analysis revealed that at least 42 proteins were modified by 2,6-DCBQ, which were mainly enriched in the reproductive system. These results highlighted the significance of covalent protein modification in 2,6-DCBQ reproductive toxicity. Fortunately, we found that catechins (a class of major components of green tea) could competitively bind to 2,6-DCBQ in vivo and in vitro, reducing the amount and type of 2,6-DCBQ-protein adducts, thereby attenuating the reproductive system damage caused by 2,6-DCBQ. This study provides new insights into 2,6-DCBQ-induced reproductive system damage and reveals a new mechanism of green tea detoxification. Moreover, these findings offer potential strategies for alleviating the harmful impacts of environmental toxicants on human health.
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Affiliation(s)
- Meixian Liu
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, 999078, Macao, China; BayRay Innovation Center, Shenzhen Bay Laboratory, Shenzhen 518132, China
| | - Zhiyuan Ning
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, 999078, Macao, China
| | - Yong Cheng
- Zhejiang Skyherb Biotechnology Inc., Huzhou 313300, China
| | - Zhiyuan Zheng
- Faculty of Pharmaceutical Sciences, Shenzhen University of Advanced Technology, Shenzhen 518107, China; Center for Cancer Immunology, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
| | - Xiaoxue Yang
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, 999078, Macao, China
| | - Ting Zheng
- Multi-omics Mass Spectrometry Core, Biomedical Research Core Facilities, Shenzhen Bay Laboratory, Shenzhen 518132, China
| | - Na Li
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, 999078, Macao, China.
| | - Jian-Lin Wu
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, 999078, Macao, China.
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Akla N, Veilleux C, Annabi B. The Chemopreventive Impact of Diet-Derived Phytochemicals on the Adipose Tissue and Breast Tumor Microenvironment Secretome. Nutr Cancer 2024; 77:9-25. [PMID: 39300732 DOI: 10.1080/01635581.2024.2401647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Revised: 08/30/2024] [Accepted: 09/02/2024] [Indexed: 09/22/2024]
Abstract
Cancer cells-derived extracellular vesicles can trigger the transformation of adipose-derived mesenchymal stem cells (ADMSC) into a pro-inflammatory, cancer-associated adipocyte (CAA) phenotype. Such secretome-mediated crosstalk between the adipose tissue and the tumor microenvironment (TME) therefore impacts tumor progression and metastatic processes. In addition, emerging roles of diet-derived phytochemicals, especially epigallocatechin-3-gallate (EGCG) among other polyphenols, in modulating exosome-mediated metabolic and inflammatory signaling pathways have been highlighted. Here, we discuss how selected diet-derived phytochemicals could alter the secretome signature as well as the crosstalk dynamics between the adipose tissue and the TME, with a focus on breast cancer. Their broader implication in the chemoprevention of obesity-related cancers is also discussed.
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Affiliation(s)
- Naoufal Akla
- Laboratoire d'Oncologie Moléculaire, Département de Chimie and CERMO-FC, Université du Québec à Montréal, Montreal, Canada
| | - Carolane Veilleux
- Laboratoire d'Oncologie Moléculaire, Département de Chimie and CERMO-FC, Université du Québec à Montréal, Montreal, Canada
| | - Borhane Annabi
- Laboratoire d'Oncologie Moléculaire, Département de Chimie and CERMO-FC, Université du Québec à Montréal, Montreal, Canada
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6
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Tzintzarov A, Boyadzhieva SS, Coelho JAP, Tsvetanova F, Petrova M, Stoev G, Yankov DS, Ugrinova I, Stateva RP. Novel Insights into the Biological Activity of Croton lechleri Twigs Extracts and Advancements in Their Sustainable Recovery. Molecules 2024; 29:4161. [PMID: 39275010 PMCID: PMC11397310 DOI: 10.3390/molecules29174161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 08/21/2024] [Accepted: 08/28/2024] [Indexed: 09/16/2024] Open
Abstract
Sangre de drago, the sap of Croton lechleri Müll. Arg. tree, has been used for centuries in traditional medicine owing to its diverse biological activities. Extracts derived from different parts of the species contain a multitude of phytochemicals with varied applications. Twigs, however, are among the least studied parts of the plant. This study unveils new biological activities of Croton lechleri twig extracts recovered by applying Soxhlet and advanced green techniques. For all extracts, total phenolic content and antioxidant activity were determined. Subsequently, four were selected, and their cytotoxic effects were assessed on both normal (HaCat) and malignant melanoma (A375) skin cell lines using the MTT assay and trypan blue exclusion assay. All showed dose-dependent cytotoxicity, with the Soxhlet ethanol extract demonstrating the highest selectivity towards A375 cells over HaCat cells. The extracts induced apoptosis and necrosis, as confirmed by Annexin V/PI dual-labeling and flow cytometry, highlighting their ability to trigger programmed cell death in cancer cells. The selective inhibition of cell cycle progression in A375 compared to HaCat observed both for Soxhlet ethanol and pressurized ethanol extracts induces cell cycle arrest at multiple points, primarily in the G1 and G2/M phases, and significantly reduces DNA synthesis as evidenced by the decrease in the S-phase population, confirmed by the EdU assay. Consequently, the Soxhlet extract composition was analyzed using LC-MS, which revealed their richness in polyphenolic compounds, particularly flavonoids from the flavonol subclass.
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Affiliation(s)
- Alexander Tzintzarov
- Institute of Molecular Biology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
| | | | - Jose A P Coelho
- Instituto Superior de Engenharia de Lisboa, Instituto Politécnico de Lisboa, Rua Conselheiro Emídio Navarro 1, 1959-007 Lisboa, Portugal
- Centro de Química Estrutural, Institute of Molecular Sciences, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049 001 Lisboa, Portugal
| | - Flora Tsvetanova
- Institute of Chemical Engineering, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
| | - Maria Petrova
- Institute of Molecular Biology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
| | - Georgi Stoev
- Institute of Molecular Biology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
| | - Dragomir S Yankov
- Institute of Chemical Engineering, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
| | - Iva Ugrinova
- Institute of Molecular Biology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
| | - Roumiana P Stateva
- Institute of Chemical Engineering, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
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7
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Wang Y. The interplay of exercise and polyphenols in cancer treatment: A focus on oxidative stress and antioxidant mechanisms. Phytother Res 2024; 38:3459-3488. [PMID: 38690720 DOI: 10.1002/ptr.8215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 04/12/2024] [Accepted: 04/14/2024] [Indexed: 05/02/2024]
Abstract
Exercise has been demonstrated to induce an elevated production of free radicals, leading to the onset of oxidative stress. Numerous studies highlight the positive impacts of aerobic exercise, primarily attributed to the increase in overall antioxidant capacity. The evidence suggests that engaging in aerobic exercise contributes to a reduction in the likelihood of advanced cancer and mortality. Oxidative stress occurs when there is an imbalance between the generation of free radicals and the collective antioxidant defense system, encompassing both enzymatic and nonenzymatic antioxidants. Typically, oxidative stress triggers the formation of reactive oxygen or nitrogen species, instigating or advancing various issues in cancers and other diseases. The pro-oxidant-antioxidant balance serves as a direct measure of this imbalance in oxidative stress. Polyphenols contain a variety of bioactive compounds, including flavonoids, flavanols, and phenolic acids, conferring antioxidant properties. Previous research highlights the potential of polyphenols as antioxidants, with documented effects on reducing cancer risk by influencing processes such as proliferation, angiogenesis, and metastasis. This is primarily attributed to their recognized antioxidant capabilities. Considering the extensive array of signaling pathways associated with exercise and polyphenols, this overview will specifically focus on oxidative stress, the antioxidant efficacy of polyphenols and exercise, and their intricate interplay in cancer treatment.
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Affiliation(s)
- Yubing Wang
- College of Physical Education, Qilu Normal University, Jinan, Shandong, China
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Khan A, Khan A, Khan MA, Malik Z, Massey S, Parveen R, Mustafa S, Shamsi A, Husain SA. Phytocompounds targeting epigenetic modulations: an assessment in cancer. Front Pharmacol 2024; 14:1273993. [PMID: 38596245 PMCID: PMC11002180 DOI: 10.3389/fphar.2023.1273993] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 11/09/2023] [Indexed: 04/11/2024] Open
Abstract
For centuries, plants have been serving as sources of potential therapeutic agents. In recent years, there has been a growing interest in investigating the effects of plant-derived compounds on epigenetic processes, a novel and captivating Frontier in the field of epigenetics research. Epigenetic changes encompass modifications to DNA, histones, and microRNAs that can influence gene expression. Aberrant epigenetic changes can perturb key cellular processes, including cell cycle control, intercellular communication, DNA repair, inflammation, stress response, and apoptosis. Such disruptions can contribute to cancer development by altering the expression of genes involved in tumorigenesis. However, these modifications are reversible, offering a unique avenue for therapeutic intervention. Plant secondary compounds, including terpenes, phenolics, terpenoids, and sulfur-containing compounds are widely found in grains, vegetables, spices, fruits, and medicinal plants. Numerous plant-derived compounds have demonstrated the potential to target these abnormal epigenetic modifications, including apigenin (histone acetylation), berberine (DNA methylation), curcumin (histone acetylation and epi-miRs), genistein (histone acetylation and DNA methylation), lycopene (epi-miRs), quercetin (DNA methylation and epi-miRs), etc. This comprehensive review highlights these abnormal epigenetic alterations and discusses the promising efficacy of plant-derived compounds in mitigating these deleterious epigenetic signatures in human cancer. Furthermore, it addresses ongoing clinical investigations to evaluate the therapeutic potential of these phytocompounds in cancer treatment, along with their limitations and challenges.
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Affiliation(s)
- Aqsa Khan
- Department of Bioscience, Faculty of Natural Sciences, Jamia Millia Islamia (A Central University), New Delhi, India
| | - Asifa Khan
- Department of Bioscience, Faculty of Natural Sciences, Jamia Millia Islamia (A Central University), New Delhi, India
| | - Mohammad Aasif Khan
- Department of Bioscience, Faculty of Natural Sciences, Jamia Millia Islamia (A Central University), New Delhi, India
- Department of Radiation Oncology, The University of Texas Health Science Centre at San Antonio, San Antonio, TX, United States
| | - Zoya Malik
- Department of Bioscience, Faculty of Natural Sciences, Jamia Millia Islamia (A Central University), New Delhi, India
| | - Sheersh Massey
- Department of Bioscience, Faculty of Natural Sciences, Jamia Millia Islamia (A Central University), New Delhi, India
| | - Rabea Parveen
- Department of Bioscience, Faculty of Natural Sciences, Jamia Millia Islamia (A Central University), New Delhi, India
| | - Saad Mustafa
- Department of Bioscience, Faculty of Natural Sciences, Jamia Millia Islamia (A Central University), New Delhi, India
| | - Anas Shamsi
- Center for Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates
| | - Syed A. Husain
- Department of Bioscience, Faculty of Natural Sciences, Jamia Millia Islamia (A Central University), New Delhi, India
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Fawzy RM, Abdel-Aziz AA, Bassiouny K, Fayed AM. Phytocompounds-based therapeutic approach: Investigating curcumin and green tea extracts on MCF-7 breast cancer cell line. J Genet Eng Biotechnol 2024; 22:100339. [PMID: 38494270 PMCID: PMC10980874 DOI: 10.1016/j.jgeb.2023.100339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2024]
Abstract
BACKGROUND Breast cancer (BC) has transcended lung cancer as the most common cancer in the world. Due to the disease's aggressiveness, rapid growth, and heterogeneity, it is crucial to investigate different therapeutic approaches for treatment. According to the World Health Organization (WHO), Plant-based therapeutics continue to be utilized as safe/non-toxic complementary or alternative treatments for cancer, even in developed countries, regardless of how cutting-edge conventional therapies are. Despite their low bioavailability, curcumin (CUR) and green tea (GT) represent safer therapeutic options. Due to their potent molecular-modulating properties on various cancer-related molecules and signaling pathways, they are considered gold-standard therapeutic agents and have been incorporated into the development of one or more therapeutic strategies of BC treatment. METHODS We investigated the modulatory role of CUR and GT extracts on significant multi molecular targets in MCF-7 BC cell line to assess their potential as BC multi-targeting agents. We analyzed the phytocompounds in GT leaves using High-performance liquid chromatography (HPLC) and Gas chromatography-mass spectrometry (GC-MS) techniques. The mRNA expression levels of Raf-1, Telomerase, Tumor necrosis factor alpha (TNF-α) and Interleukin-8 (IL-8) genes in MCF-7 cells were quantified using quantitative real-time PCR (qRT-PCR). The cytotoxicity of the extracts was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the released Lactate dehydrogenase (LDH), a valuable marker for identifying the programmed necrosis (necroptosis). Additionally, the concentrations of the necroptosis-related proinflammatory cytokines (TNF-α and IL-8) were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS In contrast to the GT, the results showed the anticancer and cytotoxic properties of CUR against MCF-7 cells, with a relatively higher level of released LDH. The CUR extract downregulated the oncogenic Raf-1, suppressed the Telomerase and upregulated the TNF-α and IL-8 genes. Results from the ELISA showed a notable increase in IL-8 and TNF-α cytokines levels after CUR treatment, which culminated after 72 h. CONCLUSIONS Among both extracts, only CUR effectively modulated the understudy molecular targets, achieving multi-targeting anticancer activity against MCF-7 cells. Moreover, the applied dosage significantly increased levels of the proinflammatory cytokines, which represent a component of the cytokines-targeting-based therapeutic strategy. However, further investigations are recommended to validate this therapeutic approach.
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Affiliation(s)
- Radwa M Fawzy
- Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute, University of Sadat City, Sadat City, Egypt.
| | - Amal A Abdel-Aziz
- Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute, University of Sadat City, Sadat City, Egypt
| | - Khalid Bassiouny
- Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute, University of Sadat City, Sadat City, Egypt
| | - Aysam M Fayed
- Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute, University of Sadat City, Sadat City, Egypt
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10
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Sharif MS, Mohseni HS, Khanavi M, Ghadami S, Jafarzadeh E, Tavajohi S, Aliebrahimi S, Ostad SN. Exploring the Synergistic Effect of Sildenafil and Green Tea Polyphenols on Breast Cancer Stem Cell-like Cells and their Parental Cells: A Potential Novel Therapeutic Approach. Anticancer Agents Med Chem 2024; 24:304-315. [PMID: 37957912 DOI: 10.2174/0118715206276925231107060329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Revised: 10/17/2023] [Accepted: 10/19/2023] [Indexed: 11/15/2023]
Abstract
BACKGROUND Many cancer studies have intensely focused on the role of diet, among other factors involved in cancer establishment. The positive effect of green tea polyphenols (GTP) on controlling breast cancer cells has been reported in several studies. Cancer stem cell-like cells (CSC-LCs) possessing self-renewal, metastatic, and drug-resistant capacities are considered prominent therapeutic targets. In many tumors, inducible nitric oxide synthase (iNOS) expression levels are high; however, they have a dual effect on breast cancer pathogenesis. OBJECTIVE This study aimed to investigate the cytotoxicity of the iNOS agonist (Sildenafil) and antagonist (LNAME), both alone and in combination with GTP, on MDA-MB-231, CD44+/CD24- CSC-LCs, and their parental cells (MCF-7). METHODS The cell viability assay has been studied using the MTT assay. To analyze drug-drug combinations, CompuSyn and Combenefit software were used. The cytotoxicity mechanism was determined using flow cytometric analysis. RESULTS L-NAME and GTP showed a synergistic effect on MDA-MB-231 and CSC-LCs. Such an effect was not observed on MCF-7. Sildenafil and GTP, on the other hand, showed synergistic cytotoxicity in all the cells mentioned above. Flow cytometric tests resulted in more than 70% apoptosis in MDA-MB-231 and MCF-7. Also, sub-G1 arrest among MCF-7 cells and a considerable decrease in ROS production by MDA-MB-231 cells following treatment with Sildenafil and GTP were observed. CONCLUSION Sildenafil, in combination with flavonoids, may be considered a novel strategy for cancer treatment.
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Affiliation(s)
- Marzie Salari Sharif
- Department of Toxicology and Pharmacology, International Campus, School of Pharmacy, Tehran University of Medical Science, Tehran, Iran
| | - Habibeh Sadat Mohseni
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahnaz Khanavi
- Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Shima Ghadami
- Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Emad Jafarzadeh
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Shohreh Tavajohi
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Shima Aliebrahimi
- Department of Artificial Intelligence, Smart University of Medical Sciences, Tehran, Iran
| | - Seyed Nasser Ostad
- Toxicology and Poisoning Research Centre, Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
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Lu J, Lin Y, Jiang J, Gao L, Shen Z, Yang C, Lin P, Kang M. Investigating the potential causal association between consumption of green tea and risk of lung cancer: a study utilizing Mendelian randomization. Front Nutr 2024; 11:1265878. [PMID: 38439922 PMCID: PMC10909932 DOI: 10.3389/fnut.2024.1265878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 02/05/2024] [Indexed: 03/06/2024] Open
Abstract
Background Lung cancer is the most common global cancer in terms of incidence and mortality. Its main driver is tobacco smoking. The identification of modifiable risk factors isa public health priority. Green tea consumption has been examined in epidemiological studies, with inconsistent findings. Thus, we aimed to apply Mendelian randomization to clarify any causal link between green tea consumption and the risk of lung cancer. Methods We utilized a two-sample Mendelian randomization (MR) approach. Genetic variants served as instrumental variables. The goal was to explore a causal link between green tea consumption and different lung cancer types. Green tea consumption data was sourced from the UK Biobank dataset, and the genetic association data for various types of lung cancer were sourced from multiple databases. Our analysis included primary inverse-variance weighted (IVW) analyses and various sensitivity test. Results No significant associations were found between green tea intake and any lung cancer subtypes, including non-small cell lung cancer (adenocarcinoma and squamous cell carcinoma) and small cell lung cancer. These findings were consistent when applying multiple Mendelian randomization methods. Conclusion Green tea does not appear to offer protective benefits against lung cancer at a population level. However, lung cancer's complex etiology and green tea's potential health benefitssuggest more research is needed. Further studies should include diverse populations, improved exposure measurements and randomized controlled trials, are warranted.
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Affiliation(s)
- Jieming Lu
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Cardio-Thoracic Surgery, Fujian Medical University, Fuzhou, China
| | - Ye Lin
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Cardio-Thoracic Surgery, Fujian Medical University, Fuzhou, China
| | - Junfei Jiang
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Cardio-Thoracic Surgery, Fujian Medical University, Fuzhou, China
| | - Lei Gao
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Cardio-Thoracic Surgery, Fujian Medical University, Fuzhou, China
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Zhimin Shen
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Cardio-Thoracic Surgery, Fujian Medical University, Fuzhou, China
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Changping Yang
- Fuqing City Hospital Affiliated to Fujian Medical University, Fuzhou, China
| | - Pinghua Lin
- Fuqing City Hospital Affiliated to Fujian Medical University, Fuzhou, China
| | - Mingqiang Kang
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Cardio-Thoracic Surgery, Fujian Medical University, Fuzhou, China
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
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Shah MA, Faheem HI, Hamid A, Yousaf R, Haris M, Saleem U, Shah GM, Alhasani RH, Althobaiti NA, Alsharif I, Silva AS. The entrancing role of dietary polyphenols against the most frequent aging-associated diseases. Med Res Rev 2024; 44:235-274. [PMID: 37486109 DOI: 10.1002/med.21985] [Citation(s) in RCA: 15] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 01/27/2023] [Accepted: 07/06/2023] [Indexed: 07/25/2023]
Abstract
Aging, a fundamental physiological process influenced by innumerable biological and genetic pathways, is an important driving factor for several aging-associated disorders like diabetes mellitus, osteoporosis, cancer, and neurodegenerative diseases including Alzheimer's and Parkinson's diseases. In the modern era, the several mechanisms associated with aging have been deeply studied. Treatment and therapeutics for age-related diseases have also made considerable advances; however, for the effective and long-lasting treatment, nutritional therapy particularly including dietary polyphenols from the natural origin are endorsed. These dietary polyphenols (e.g., apigenin, baicalin, curcumin, epigallocatechin gallate, kaempferol, quercetin, resveratrol, and theaflavin), and many other phytochemicals target certain molecular, genetic mechanisms. The most common pathways of age-associated diseases are mitogen-activated protein kinase, reactive oxygen species production, nuclear factor kappa light chain enhancer of activated B cells signaling pathways, metal chelation, c-Jun N-terminal kinase, and inflammation. Polyphenols slow down the course of aging and help in combatting age-linked disorders. This exemplified in the form of clinical trials on specific dietary polyphenols in various aging-associated diseases. With this context in mind, this review reveals the new insights to slow down the aging process, and consequently reduce some classic diseases associated with age such as aforementioned, and targeting age-associated diseases by the activities of dietary polyphenols of natural origin.
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Affiliation(s)
| | - Hafiza Ishmal Faheem
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, Pakistan
| | - Ayesha Hamid
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, Pakistan
| | - Rimsha Yousaf
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, Pakistan
| | - Muhammad Haris
- Faculty of Pharmaceutical Sciences, Universiteit Gent, Ghent, Belgium
| | - Uzma Saleem
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, Pakistan
| | - Ghulam Mujtaba Shah
- Department of Botany, Faculty of Health and Biological Sciences, Hazara University, Mansehra, Pakistan
| | - Reem H Alhasani
- Department of Biology, Faculty of Applied Science, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Norah A Althobaiti
- Department of Biology, College of Science and Humanities, Shaqra University, Al-Quwaiiyah, Saudi Arabia
| | - Ifat Alsharif
- Department of Biology, Jamoum University College, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Ana Sanches Silva
- National Institute for Agrarian and Veterinary Research (INIAV), I.P., Rua dos Lágidos, Lugar da Madalena, Vairão, Vila do Conde, Portugal
- University of Coimbra, Faculty of Pharmacy, Polo III, Azinhaga de St Comba, Coimbra, Portugal
- Centre for Animal Science Studies (CECA), ICETA, University of Porto, Porto, Portugal
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14
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Gorain B, Karmakar V, Sarkar B, Dwivedi M, Leong JTL, Toh JH, Seah E, Ling KY, Chen KY, Choudhury H, Pandey M. Biomacromolecule-based nanocarrier strategies to deliver plant-derived bioactive components for cancer treatment: A recent review. Int J Biol Macromol 2023; 253:126623. [PMID: 37657573 DOI: 10.1016/j.ijbiomac.2023.126623] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 08/25/2023] [Accepted: 08/29/2023] [Indexed: 09/03/2023]
Abstract
The quest for safe chemotherapy has attracted researchers to explore anticancer potential of herbal medicines. Owing to upsurging evidence of herbal drug's beneficial effects, hopes are restored for augmenting survival rates in cancer patients. However, phytoconstituents confronted severe limitations in terms of poor absorption, low-stability, and low bioavailability. Along with toxicity issues associated with phytoconstituents, quality control and limited regulatory guidance also hinder the prevalence of herbal medicines for cancer therapy. Attempts are underway to exploit nanocarriers to circumvent the limitations of existing and new herbal drugs, where biological macromolecules (e.g., chitosan, hyaluronic acid, etc.) are established highly effective in fabricating nanocarriers and cancer targeting. Among the discussed nanocarriers, liposomes and micelles possess properties to cargo hydro- and lipophilic herbal constituents with surface modification for targeted delivery. Majorly, PEG, transferrin and folate are utilized for surface modification to improve bioavailability, circulation time and targetability. The dendrimer and carbon nanotubes responded in high-loading efficiency of phytoconstituent; whereas, SLN and nanoemulsions are suited carriers for lipophilic extracts. This review emphasized unveiling the latent potential of herbal drugs along with discussing on extended benefits of nanocarriers-based delivery of phytoconstituents for safe cancer therapy owing to enhanced clinical and preclinical outcomes without compromising safety.
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Affiliation(s)
- Bapi Gorain
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835215, India.
| | - Varnita Karmakar
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835215, India
| | - Biswatrish Sarkar
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835215, India
| | - Monika Dwivedi
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835215, India
| | - Janelle Tsui Lyn Leong
- School of Pharmacy, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya 47500, Selangor, Malaysia
| | - Jing Hen Toh
- School of Pharmacy, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya 47500, Selangor, Malaysia
| | - Even Seah
- School of Pharmacy, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya 47500, Selangor, Malaysia
| | - Kang Yi Ling
- School of Pharmacy, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya 47500, Selangor, Malaysia
| | - Kah Yee Chen
- School of Pharmacy, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya 47500, Selangor, Malaysia
| | - Hira Choudhury
- Department of Pharmaceutical Technology, School of Pharmacy, International Medical University, Bukit Jalil, 57000 Kuala Lumpur, Malaysia
| | - Manisha Pandey
- Department of Pharmaceutical Sciences, Central University of Haryana, SSH 17, Jant, Haryana 123031, India.
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15
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Wang G, Wang J, Momeni MR. Epigallocatechin-3-gallate and its nanoformulation in cervical cancer therapy: the role of genes, MicroRNA and DNA methylation patterns. Cancer Cell Int 2023; 23:335. [PMID: 38129839 PMCID: PMC10740301 DOI: 10.1186/s12935-023-03161-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Accepted: 11/22/2023] [Indexed: 12/23/2023] Open
Abstract
Green tea, a popular and healthy nonalcoholic drink consumed globally, is abundant in natural polyphenols. One of these polyphenols is epigallocatechin-3-gallate (EGCG), which offers a range of health benefits, such as metabolic regulation, antioxidant properties, anti-inflammatory effects, and potential anticancer properties. Clinical research has shown that EGCG can inhibit cancers in the male and female reproductive systems, including ovarian, cervical, endometrial, breast, testicular, and prostate cancers. Further research on cervical cancer has revealed the crucial role of epigenetic mechanisms in the initiation and progression of this type of cancer. These include changes to the DNA, histones, and non-coding RNAs, such as microRNAs. These changes are reversible and can occur even before genetic mutations, making them a potential target for intervention therapies. One promising approach to cancer prevention and treatment is the use of specific agents (known as epi-drugs) that target the cancer epigenome or epigenetic dysregulation. Phytochemicals, a group of diverse molecules, have shown potential in modulating cancer processes through their interaction with the epigenetic machinery. Among these, green tea and its main polyphenol EGCG have been extensively studied. This review highlights the therapeutic effects of EGCG and its nanoformulations on cervical cancer. It also discusses the epigenetic events involved in cervical cancer, such as DNA methylation and microRNA dysregulation, which may be affected by EGCG.
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Affiliation(s)
- Guichun Wang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Jinyi Wang
- School of Clinical Medicine, Tsinghua University, Beijing, 100084, China.
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16
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Almaguer G, Almaguer-Vargas G, Molina-Trinidad EM, Becerril-Flores MA, Montejano B, Madrigal-Santillan E, Hernández-Ceruelos A, Figueroa-Gutiérrez AH, Montejano E, Montejano-Rodríguez JR. Antitumor Effect of Epigallocatechin Gallate and Vincristine in Mice with L5178Y Lymphoma. PLANTS (BASEL, SWITZERLAND) 2023; 12:3757. [PMID: 37960113 PMCID: PMC10647321 DOI: 10.3390/plants12213757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 09/24/2023] [Accepted: 10/20/2023] [Indexed: 11/15/2023]
Abstract
The main objective of research into new therapies is the search for more efficacy and fewer toxic effects in cancer treatments. On one hand, vincristine (VCR) is a chemotherapeutic used in different kinds of tumors. On the other hand, epigallocatechin gallate (EGCG) is a green tea metabolite that has shown an antineoplastic effect in diverse investigations, so the objective of this work is to evaluate the antitumor effects of the EGCG/VCR combination on tumor volume and survival. To achieve this objective, the solid model of lymphoma L5178Y was used in BALB/c mice with different doses of VCR, EGCG, and their combination allowed tumor growth and survival time recording. After tumor collection, measurements, and immunohistochemistry for p53, Bcl2, and Cyclin D1 were performed. The results showed that the EGCG/vincristine combination had a greater antitumor effect than those effects of vincristine and EGCG. It can be attributed to the fact that the greatest inhibition of Bcl2 was present in gathering of EGCG harvest with vincristine. Therefore, the combination of EGCG with vincristine has a better antineoplastic effect by inhibiting tumor development and increasing survival on both substances independently.
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Affiliation(s)
- Georgina Almaguer
- Institute of Health Sciences, Autonomous University of the State of Hidalgo, Ex-Hacienda de la Concepción, Tilcuautla 42183, Mexico
| | - Gustavo Almaguer-Vargas
- Plant Breeding Department, Horticulture Institute, Chapingo Autonomous University, Federal Highway Mexico-Texcoco km 38.5, Chapingo, Texcoco 56230, Mexico
| | - Eva María Molina-Trinidad
- Institute of Health Sciences, Autonomous University of the State of Hidalgo, Ex-Hacienda de la Concepción, Tilcuautla 42183, Mexico
| | - Marco Antonio Becerril-Flores
- Institute of Health Sciences, Autonomous University of the State of Hidalgo, Ex-Hacienda de la Concepción, Tilcuautla 42183, Mexico
| | - Brenda Montejano
- Department of Pharmacy, Hospital San José, Santiago de Querétaro 76180, Mexico
| | - Eduardo Madrigal-Santillan
- Institute of Health Sciences, Autonomous University of the State of Hidalgo, Ex-Hacienda de la Concepción, Tilcuautla 42183, Mexico
| | - Alejandra Hernández-Ceruelos
- Institute of Health Sciences, Autonomous University of the State of Hidalgo, Ex-Hacienda de la Concepción, Tilcuautla 42183, Mexico
| | - Ana Hilda Figueroa-Gutiérrez
- Institute of Health Sciences, Autonomous University of the State of Hidalgo, Ex-Hacienda de la Concepción, Tilcuautla 42183, Mexico
| | - Ethoan Montejano
- Interdisciplinary Professional Unit of Biotechnology IPN, National Polytechnic Institute, Av. Acueducto, La Laguna Ticoman, Gustavo A. Madero, Mexico City 07340, Mexico;
| | - José Ramón Montejano-Rodríguez
- Institute of Health Sciences, Autonomous University of the State of Hidalgo, Ex-Hacienda de la Concepción, Tilcuautla 42183, Mexico
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17
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Farghadani R, Naidu R. The anticancer mechanism of action of selected polyphenols in triple-negative breast cancer (TNBC). Biomed Pharmacother 2023; 165:115170. [PMID: 37481930 DOI: 10.1016/j.biopha.2023.115170] [Citation(s) in RCA: 37] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 07/10/2023] [Accepted: 07/12/2023] [Indexed: 07/25/2023] Open
Abstract
Breast cancer is a leadingcause of cancer-related deaths in women globally, with triple-negative breast cancer (TNBC) being an aggressive subtype that lacks targeted therapies and is associated with a poor prognosis. Polyphenols, naturally occurring compounds in plants, have been investigated as a potential therapeutic strategy for TNBC. This review provides an overview of the anticancer effects of polyphenols in TNBC and their mechanisms of action. Several polyphenols, including resveratrol, quercetin, kaempferol, genistein, epigallocatechin-3-gallate, apigenin, fisetin, hesperetin and luteolin, have been shown to inhibit TNBC cell proliferation, induce cell cycle arrest, promote apoptosis, and suppress migration/invasion in preclinical models. The molecular mechanisms underlying their anticancer effects involve the modulation of several signalling pathways, such as PI3K/Akt, MAPK, STATT, and NF-κB pathways. Polyphenols also exhibit synergistic effects with chemotherapy drugs, making them promising candidates for combination therapy. The review also highlights clinical trials investigating the potential use of polyphenols, individually or in combination therapy, against breast cancer. This review deepens the under-standing of the mechanism of action of respective polyphenols and provides valuable insights into the potential use of polyphenols as a therapeutic strategy for TNBC, and lays the groundwork for future research in this area.
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Affiliation(s)
- Reyhaneh Farghadani
- Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Selangor Darul Ehsan 47500, Malaysia.
| | - Rakesh Naidu
- Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Selangor Darul Ehsan 47500, Malaysia.
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18
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Zhou Y, Zhang T, Wang S, Yang R, Jiao Z, Lu K, Li H, Jiang W, Zhang X. Targeting of HBP1/TIMP3 axis as a novel strategy against breast cancer. Pharmacol Res 2023; 194:106846. [PMID: 37414199 DOI: 10.1016/j.phrs.2023.106846] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 06/30/2023] [Accepted: 06/30/2023] [Indexed: 07/08/2023]
Abstract
Malignant proliferation and metastasis are the main causes of breast cancer death. The transcription factor high mobility group (HMG) box-containing protein 1 (HBP1) is an important tumor suppressor whose deletion or mutation is closely related to the appearance of tumors. Here, we investigated the role of HBP1 in breast cancer suppression. HBP1 enhances the activity of the tissue inhibitors of metalloproteinases 3 (TIMP3) promoter, thereby increasing protein and mRNA levels of TIMP3. TIMP3 increases the phosphatase and tensin homolog (PTEN) protein level by inhibiting its degradation and acts as a metalloproteinase inhibitor to inhibit the protein levels of MMP2/9. In this study, we demonstrated that the HBP1/TIMP3 axis plays a crucial role in inhibiting the tumorigenesis of breast cancer. HBP1 deletion interferes with the regulation of the axis and induces the occurrence and malignant progression of breast cancer. In addition, the HBP1/TIMP3 axis promotes the sensitivity of breast cancer to radiation therapy and hormone therapy. Our study opens new perspectives on the treatment and prognosis of breast cancer.
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Affiliation(s)
- Yue Zhou
- Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Peking University Health Science Center, Beijing 100191, PR China
| | - Tongjia Zhang
- Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Peking University Health Science Center, Beijing 100191, PR China
| | - Shujie Wang
- Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Peking University Health Science Center, Beijing 100191, PR China
| | - Ruixiang Yang
- Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Peking University Health Science Center, Beijing 100191, PR China
| | - Zitao Jiao
- Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Peking University Health Science Center, Beijing 100191, PR China
| | - Kejia Lu
- Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Peking University Health Science Center, Beijing 100191, PR China
| | - Hui Li
- Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Peking University Health Science Center, Beijing 100191, PR China
| | - Wei Jiang
- Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Peking University Health Science Center, Beijing 100191, PR China
| | - Xiaowei Zhang
- Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Peking University Health Science Center, Beijing 100191, PR China.
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Tian X, Xu J, Ye Y, Xiao X, Yan L, Yu S, Cai4 J, Du Q, Dong X, Zhou L, Shan L, Yuan Q. Gallic acid in theabrownin suppresses cell proliferation and migration in non‑small cell lung carcinoma via autophagy inhibition. Oncol Lett 2023; 26:294. [PMID: 37274480 PMCID: PMC10236267 DOI: 10.3892/ol.2023.13880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Accepted: 03/17/2023] [Indexed: 06/06/2023] Open
Abstract
The bioactive extract of green tea, theabrownin (TB), is known to exhibit pro-apoptotic and antitumor effects on non-small cell lung cancer (NSCLC). Gallic acid (GA) is a crucial component of TB; however, its mechanism of action in NSCLC has been rarely studied. To date, little attention has been paid to the anti-NSCLC activity of GA. Therefore, the present study investigated the effects of GA in vivo and in vitro. Cell Counting Kit (CCK)-8 assay, DAPI staining and flow cytometry, wound-healing assay and western blotting were used to assess cell viability, apoptosis, migration and protein expression, respectively. In addition, a xenograft model was generated, and TUNEL assay and immunohistochemistry analysis were performed. The CCK-8 data showed that the viability of H1299 cells was significantly inhibited by GA in a dose- and time-dependent manner. DAPI staining, Annexin-V/PI staining and wound-healing data showed that GA exerted pro-apoptotic and anti-migratory effects on H1299 cells in a dose-dependent manner. Furthermore, the results of western blotting showed that GA significantly upregulated the levels of pro-apoptotic proteins [cleaved (c-)PARP, c-caspase8, c-caspase-9 and the ratio of γ-H2A.X/H2A.X]. In vivo data confirmed the antitumor effect of GA through apoptosis induction in an autophagy-dependent manner. In conclusion, the present study confirmed the anti-proliferative, pro-apoptotic and anti-migratory effects of GA against NSCLC in vitro and in vivo, providing considerable evidence for its potential as a novel candidate for the treatment of NSCLC.
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Affiliation(s)
- Xue Tian
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
- The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
| | - Jiaan Xu
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
- The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
| | - Yonghua Ye
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
- The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
| | - Xiujuan Xiao
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
- The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
| | - Li Yan
- Cell Resource Bank and Integrated Cell Preparation Center of Xiaoshan District, Hangzhou Regional Cell Preparation Center (Shangyu Biotechnology Co., Ltd.), Hangzhou, Zhejiang 311200, P.R. China
| | - Shihui Yu
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
- The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
| | - Jianyong Cai4
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
| | - Quan Du
- Department of Neurosurgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China
| | - Xiaoqiao Dong
- Department of Neurosurgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China
| | - Li Zhou
- The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
- Cell Resource Bank and Integrated Cell Preparation Center of Xiaoshan District, Hangzhou Regional Cell Preparation Center (Shangyu Biotechnology Co., Ltd.), Hangzhou, Zhejiang 311200, P.R. China
| | - Letian Shan
- The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
- Cell Resource Bank and Integrated Cell Preparation Center of Xiaoshan District, Hangzhou Regional Cell Preparation Center (Shangyu Biotechnology Co., Ltd.), Hangzhou, Zhejiang 311200, P.R. China
| | - Qiang Yuan
- College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
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20
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Lee H, Hyun Jeong J, Lee T, Chong Y, Choo H, Lee S. Identification of (-)-Epigallocateshin Gallate Derivatives promoting innate immune activation via 2' 3'-cyclic GMP-AMP-stimulator of interferon genes pathway. Bioorg Med Chem Lett 2023; 90:129325. [PMID: 37182610 DOI: 10.1016/j.bmcl.2023.129325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 05/04/2023] [Accepted: 05/09/2023] [Indexed: 05/16/2023]
Abstract
(-)-Epigallocatehin-3-gallate (EGCG) is a catechin derived from green tea, which has been widely studied for its anti-oxidant and anti-tumor properties. Although EGCG plays important roles in various biological processes, the its effect on the immune system is not fully understood. In this study, we investigated the potential of EGCG as an activator of the stimulator of interferon genes (STING) pathway in the immune system. The cyclic GMP-AMP synthase (cGAS)-2'-3'-cyclic GMP-AMP (cGAMP)-STING pathway is crucial in the innate immune response to microbial infections, autoimmunity, and anticancer immunity. We confirmed that EGCG enhanced the immune response of cGAMP and identified E2 from 13 synthetic derivatives of EGCG. E2 specifically activated the interferon (IFN) signaling pathway specifically through STING- and cGAMP-dependent mechanisms. These results demonstrate the potential of EGCG and its derivatives as new STING activators that can stimulate the type I interferon response by boosting cGAMP-mediated STING activity.
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Affiliation(s)
- Hyelim Lee
- Brain Science Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea
| | - Jeong Hyun Jeong
- Brain Science Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea
| | - Taegum Lee
- Department of Integrative Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul 05029, Korea
| | - Youhoon Chong
- Department of Integrative Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul 05029, Korea
| | - Hyunah Choo
- Brain Science Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea; Division of Bio-Medical Science & Technology, KIST School, University of Science and Technology, Seoul 02792, Republic of Korea
| | - Sanghee Lee
- Brain Science Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea; Department for HY-KIST Bio-convergence, Hanyang University, Seoul, Republic of Korea.
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Mir RH, Mir PA, Uppal J, Chawla A, Patel M, Bardakci F, Adnan M, Mohi-ud-din R. Evolution of Natural Product Scaffolds as Potential Proteasome Inhibitors in Developing Cancer Therapeutics. Metabolites 2023; 13:metabo13040509. [PMID: 37110167 PMCID: PMC10142660 DOI: 10.3390/metabo13040509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 03/28/2023] [Accepted: 03/29/2023] [Indexed: 04/05/2023] Open
Abstract
Homeostasis between protein synthesis and degradation is a critical biological function involving a lot of precise and intricate regulatory systems. The ubiquitin-proteasome pathway (UPP) is a large, multi-protease complex that degrades most intracellular proteins and accounts for about 80% of cellular protein degradation. The proteasome, a massive multi-catalytic proteinase complex that plays a substantial role in protein processing, has been shown to have a wide range of catalytic activity and is at the center of this eukaryotic protein breakdown mechanism. As cancer cells overexpress proteins that induce cell proliferation, while blocking cell death pathways, UPP inhibition has been used as an anticancer therapy to change the balance between protein production and degradation towards cell death. Natural products have a long history of being used to prevent and treat various illnesses. Modern research has shown that the pharmacological actions of several natural products are involved in the engagement of UPP. Over the past few years, numerous natural compounds have been found that target the UPP pathway. These molecules could lead to the clinical development of novel and potent anticancer medications to combat the onslaught of adverse effects and resistance mechanisms caused by already approved proteasome inhibitors. In this review, we report the importance of UPP in anticancer therapy and the regulatory effects of diverse natural metabolites, their semi-synthetic analogs, and SAR studies on proteasome components, which may aid in discovering a new proteasome regulator for drug development and clinical applications.
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Affiliation(s)
- Reyaz Hassan Mir
- Pharmaceutical Chemistry Division, Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal, Srinagar 190006, Jammu and Kashmir, India
| | - Prince Ahad Mir
- Khalsa College of Pharmacy, G.T. Road, Amritsar 143001, Punjab, India
| | - Jasreen Uppal
- Khalsa College of Pharmacy, G.T. Road, Amritsar 143001, Punjab, India
| | - Apporva Chawla
- Khalsa College of Pharmacy, G.T. Road, Amritsar 143001, Punjab, India
| | - Mitesh Patel
- Department of Biotechnology, Parul Institute of Applied Sciences and Centre of Research for Development, Parul University, Vadodara 391760, Gujarat, India
| | - Fevzi Bardakci
- Department of Biology, College of Science, University of Ha’il, Ha’il P.O. Box 2440, Saudi Arabia
| | - Mohd Adnan
- Department of Biology, College of Science, University of Ha’il, Ha’il P.O. Box 2440, Saudi Arabia
| | - Roohi Mohi-ud-din
- Department of General Medicine, Sher-I-Kashmir Institute of Medical Sciences (SKIMS), Srinagar 190001, Jammu and Kashmir, India
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22
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Karimi-Shahri M, Alalikhan A, Hashemian P, Hashemzadeh A, Javid H. The applications of epigallocatechin gallate (EGCG)-nanogold conjugate in cancer therapy. NANOTECHNOLOGY 2023; 34:212001. [PMID: 36535007 DOI: 10.1088/1361-6528/acaca3] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Accepted: 12/18/2022] [Indexed: 06/17/2023]
Abstract
Cancer has recently increased the death toll worldwide owing to inadequate therapy and decreased drug bioavailability. Long-term and untargeted chemotherapeutic exposure causes toxicity to healthy cells and drug resistance. These challenges necessitate the development of new methods to increase drug efficacy. Nanotechnology is an emerging field in the engineering of new drug delivery platforms. The phytochemical epigallocatechin gallate (EGCG), the main component of green tea extract and its most bioactive component, offers novel approaches to cancer cell eradication. The current review focuses on the nanogold-based carriers containing EGCG, with an emphasis on the chemotherapeutic effects of EGCG in cancer treatment. The nanoscale vehicle may improve the EGCG solubility and bioavailability while overcoming constraints and cellular barriers. This article reviewed the phytochemical EGCG-based gold nanoplatforms and their major anticancer applications, both individually, and in combination therapy in a few cases.
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Affiliation(s)
- Mehdi Karimi-Shahri
- Department of Pathology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Pathology, School of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran
| | - Abbas Alalikhan
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Pedram Hashemian
- Jahad Daneshgahi Research Committee, Jahad Daneshgahi Institute, Mashhad, Iran
| | - Alireza Hashemzadeh
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Medical Laboratory Sciences, Varastegan Institute for Medical Sciences, Mashhad, Iran
| | - Hossein Javid
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Medical Laboratory Sciences, Varastegan Institute for Medical Sciences, Mashhad, Iran
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23
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Sahadevan R, Binoy A, Vechalapu SK, Nanjan P, Sadhukhan S. In situ global proteomics profiling of EGCG targets using a cell-permeable and Click-able bioorthogonal probe. Int J Biol Macromol 2023; 237:123991. [PMID: 36907293 DOI: 10.1016/j.ijbiomac.2023.123991] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 03/01/2023] [Accepted: 03/05/2023] [Indexed: 03/12/2023]
Abstract
Despite possessing a wide spectrum of biological activities, molecular targets of EGCG remain elusive and as a result, its precise mode of action is still unknown. Herein, we have developed a novel cell-permeable and Click-able bioorthogonal probe for EGCG, YnEGCG for in situ detection and identification of its interacting proteins. The strategic structural modification on YnEGCG allowed it to retain innate biological activities of EGCG (IC50 59.52 ± 1.14 μM and 9.07 ± 0.01 μM for cell viability and radical scavenging activity, respectively). Chemoproteomics profiling identified 160 direct EGCG targets, with H:L ratio ≥ 1.10 from the list of 207 proteins, including multiple new proteins that were previously unknown. The targets were broadly distributed in various subcellular compartments suggesting a polypharmacological mode of action of EGCG. GO analysis revealed that the primary targets belonged to the enzymes that regulate key metabolic processes including glycolysis and energy homeostasis, also the cytoplasm (36 %) and mitochondria (15.6 %) contain the majority of EGCG targets. Further, we validated that EGCG interactome was closely associated with apoptosis indicating its role in inducing toxicity in cancer cells. For the first time, this in situ chemoproteomics approach could identify a direct and specific EGCG interactome under physiological conditions in an unbiased manner.
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Affiliation(s)
- Revathy Sahadevan
- Department of Chemistry, Indian Institute of Technology Palakkad, Kerala, India
| | - Anupama Binoy
- Department of Chemistry, Indian Institute of Technology Palakkad, Kerala, India
| | - Sai K Vechalapu
- Department of Chemistry, Indian Institute of Technology Kanpur, Uttar Pradesh, India
| | - Pandurangan Nanjan
- Department of Chemistry, Indian Institute of Technology Palakkad, Kerala, India
| | - Sushabhan Sadhukhan
- Department of Chemistry, Indian Institute of Technology Palakkad, Kerala, India; Physical & Chemical Biology Laboratory, Indian Institute of Technology Palakkad, Kerala, India; Department of Biological Sciences & Engineering, Indian Institute of Technology Palakkad, Kerala, India.
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24
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Gor R, Ramachandran I, Ramalingam S. Targeting the Cancer Stem Cells in Endocrine Cancers with Phytochemicals. Curr Top Med Chem 2022; 22:2589-2597. [PMID: 36380414 DOI: 10.2174/1567205020666221114112814] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Revised: 09/11/2022] [Accepted: 10/13/2022] [Indexed: 11/17/2022]
Abstract
Endocrine cancer is an uncontrolled growth of cells in the hormone-producing glands. Endocrine cancers include the adrenal, thyroid, parathyroid, pancreas, pituitary, and ovary malignancy. Recently, there is an increase in the incidence of the most common endocrine cancer types, namely pancreatic and thyroid cancers. Cancer stem cells (CSCs) of endocrine tumors have received more attention due to their role in cancer progression, therapeutic resistance, and cancer relapse. Phytochemicals provide several health benefits and are effective in the treatment of various diseases including cancer. Therefore, finding the natural phytochemicals that target the CSCs will help to improve cancer patients' prognosis and life expectancy. Phytochemicals have been shown to have anticancer properties and are very effective in treating various cancer types. Curcumin is a common polyphenol found in turmeric, which has been shown to promote cellular drug accumulation and increase the effectiveness of chemotherapy. Moreover, various other phytochemicals such as resveratrol, genistein, and apigenin are effective against different endocrine cancers by regulating the CSCs. Thus, phytochemicals have emerged as chemotherapeutics that may have significance in preventing and treating the endocrine cancers.
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Affiliation(s)
- Ravi Gor
- Department of Genetic Engineering, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu, 603203, Tamil Nadu, India
| | - Ilangovan Ramachandran
- Department of Endocrinology, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600113, Tamil Nadu, India
| | - Satish Ramalingam
- Department of Genetic Engineering, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu, 603203, Tamil Nadu, India
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25
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Trisha AT, Shakil MH, Talukdar S, Rovina K, Huda N, Zzaman W. Tea Polyphenols and Their Preventive Measures against Cancer: Current Trends and Directions. Foods 2022; 11:3349. [PMID: 36359962 PMCID: PMC9658101 DOI: 10.3390/foods11213349] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Revised: 09/11/2022] [Accepted: 10/13/2022] [Indexed: 07/30/2023] Open
Abstract
Cancer is exerting an immense strain on the population and health systems all over the world. Green tea because of its higher simple catechin content (up to 30% on dry weight basis) is greatly popular as an anti-cancer agent which is found to reduce the risks of cancer as well as a range of other diseases. In addition, several in vitro and in vivo studies have shown that green tea possesses copious health benefits like anti-diabetic, anti-obese, anti-inflammatory, neuro-protective, cardio-protective, etc. This review highlights the anti-carcinogenic effects of green tea catechins integrating the recent information to gain a clear concept. Special emphasis was given to the effectiveness of green tea polyphenols (GTP) in the prevention of cancer. Overall, green tea has been found to be effective to reduce the risks of breast cancer, ovarian cancer, liver cancer, colorectal cancer, skin cancer, prostate cancer, oral cancer, etc. However, sufficient information was not found to support that green tea consumption reduces the risk of lung cancer, esophageal cancer, or stomach cancer. The exciting data integrated into this article will increase interest in future researchers to garner more fruitful information on the relevant topics.
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Affiliation(s)
- Anuva Talukder Trisha
- Department of Food Engineering and Tea Technology, Shahjalal University of Science and Technology, Sylhet 3114, Bangladesh
| | - Mynul Hasan Shakil
- Department of Food Engineering and Tea Technology, Shahjalal University of Science and Technology, Sylhet 3114, Bangladesh
| | - Suvro Talukdar
- Department of Food Engineering and Tea Technology, Shahjalal University of Science and Technology, Sylhet 3114, Bangladesh
| | - Kobun Rovina
- Faculty of Food Science and Nutrition, Universiti Malaysia Sabah, Kota Kinabalu 88400, Sabah, Malaysia
| | - Nurul Huda
- Faculty of Food Science and Nutrition, Universiti Malaysia Sabah, Kota Kinabalu 88400, Sabah, Malaysia
| | - Wahidu Zzaman
- Department of Food Engineering and Tea Technology, Shahjalal University of Science and Technology, Sylhet 3114, Bangladesh
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26
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Apple Polyphenol Diet Extends Lifespan, Slows down Mitotic Rate and Reduces Morphometric Parameters in Drosophila Melanogaster: A Comparison between Three Different Apple Cultivars. Antioxidants (Basel) 2022; 11:antiox11112086. [DOI: 10.3390/antiox11112086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 10/14/2022] [Accepted: 10/19/2022] [Indexed: 11/16/2022] Open
Abstract
Plant-derived polyphenols exhibit beneficial effects on physiological and pathological processes, including cancer and neurodegenerative disorders, mainly because of their antioxidant activity. Apples are highly enriched in these compounds, mainly in their peel. The Tuscia Red (TR) apple variety exhibits the peculiar characteristic of depositing high quantities of polyphenols in the pulp, the edible part of the fruit. Since polyphenols, as any natural product, cannot be considered a panacea per se, in this paper, we propose to assess the biological effects of TR flesh extracts, in comparison with two commercial varieties, in a model system, the insect Drosophila melanogaster, largely recognized as a reliable system to test the in vivo effects of natural and synthetic compounds. We performed a comparative, qualitative and quantitative analysis of the polyphenol compositions of the three cultivars and found that TR flesh shows the highest content of polyphenols, and markedly, anthocyanins. Then, we focused on their effects on a panel of physiological, morphometrical, cellular and behavioral phenotypes in wild-type D. melanogaster. We found that all the apple polyphenol extracts showed dose-dependent effects on most of the phenotypes we considered. Remarkably, all the varieties induced a strong relenting of the cell division rate.
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27
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Chu KO, Man GCW, Hung SW, Chan TH, Lee WYT, Chan KP, Pang CP, Wang CC. Determination of (-)-epigallocatechin-3-gallate octaacetate and its metabolites in plasma of rats for pharmacokinetic study by ultra-performance-liquid-chromatography coupled to quadrupole-time-of-flight-mass-spectrometry. Front Pharmacol 2022; 13:1025053. [PMID: 36304154 PMCID: PMC9592989 DOI: 10.3389/fphar.2022.1025053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 09/22/2022] [Indexed: 11/13/2022] Open
Abstract
(-)-Epigallocatechin-gallate octaacetate (pro-EGCG), a prodrug of epigallocatechin-gallate (EGCG), has been used for pre-clinical study for the treatment of endometriosis. A validated analytical method has been developed for the determination of plasma pro-EGCG and its metabolites after oral administration using ultra-performance-liquid-chromatography coupled to quadrupole-time-of-flight-mass-spectrometry (UPLC-Qtof-MS). This method is more robust, rapid, sensitive, simpler, and able to detect pro-EGCG metabolites compared to our previous method. Pro-EGCG in the plasma was stabilized from rapid degradation by formic acid, extracted by isopropanol/methyl-tert-butyl ether mixture, separated by UPLC core column, and quantified by an exact mass method with Qtof-MS. The lower limit of quantification (LLOQ), intra-day and inter-day precision, and accuracy for the range of 0.01–2.5 μg/mL were within acceptable limits. The sensitivity was improved by 25 folds using pro-EGCG ammonium adduct [M + NH4]+. This is the first report on the pharmacokinetics of oral administration with maximum-concentration (Cmax) was 0.067 ± 0.04 μg/mL, time-of-maximum-concentration (Tmax) was 1.33 h, area-under-curve (AUC) was 0.20 ± 0.05 h × µg/mL, and elimination-rate was 0.20 ± 0.11 hr−1. The pharmacokinetic profiles of pro-EGCG metabolites, (-)-epigallocatechin-gallate (EGCG) diacetates and EGCG triacetates, were also presented. This method is robust, rapid, and sensitive for the pharmacokinetic study of pro-EGCG and metabolites.
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Affiliation(s)
- Kai On Chu
- Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Shatin, China
- Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Shatin, China
| | - Gene Chi Wai Man
- Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Shatin, China
| | - Sze Wan Hung
- Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Shatin, China
| | - Tak Hang Chan
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China
- Department of Chemistry, McGill University, Montreal, QC, Canada
| | | | - Kwok Ping Chan
- Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Shatin, China
| | - Chi Pui Pang
- Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Shatin, China
- Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou, China
| | - Chi Chiu Wang
- Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Shatin, China
- Li Ka Shing Institute of Health Sciences; and School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, China
- *Correspondence: Chi Chiu Wang,
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28
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Banerjee S, Mandal AKA. Role of epigallocatechin-3- gallate in the regulation of known and novel microRNAs in breast carcinoma cells. Front Genet 2022; 13:995046. [PMID: 36276982 PMCID: PMC9582282 DOI: 10.3389/fgene.2022.995046] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 09/15/2022] [Indexed: 11/24/2022] Open
Abstract
Breast cancer comprises 30% of all cancer cases among the world’s women population. MicroRNAs are small, endogenous, non-coding RNAs that regulate cell proliferating and apoptotic pathways by modulating expressions of related genes. Phytochemicals like epigallocatechin-3-gallate (EGCG) are known to have a chemotherapeutic effect on cancer often through the regulation of microRNAs. The aim is to find out the key known and novel miRNAs, which are controlled by EGCG in breast cancer cell line MDA-MB-231. Next-generation sequencing (NGS) revealed 1,258 known and 330 novel miRNAs from untreated and 83 μM EGCG (IC50 value of EGCG) treated cells. EGCG modulated 873 known and 47 novel miRNAs in the control vs. treated sample. The hypothesis of EGCG being a great modulator of miRNAs that significantly control important cancer-causing pathways has been established by analyzing with Kyoto Encyclopedia of Genes and Genomes (KEGG) and Protein Analysis Through Evolutionary Relationships (PANTHER) database. Validation of known and novel miRNA expression differences in untreated vs. treated cells was done using qPCR. From this study, a few notable miRNAs were distinguished that can be used as diagnostics as well as prognostic markers for breast cancer.
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29
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Colomeu TC, de Figueiredo D, de Matos da Silva P, Fernandes LGR, Zollner RDL. Antiproliferative and Pro-Oxidant Effect of Polyphenols in Aqueous Leaf Extract of Passiflora alata Curtis on Activated T Lymphocytes from Non-Obese Diabetic (NOD SHILT/J) Mice. Antioxidants (Basel) 2022; 11:antiox11081503. [PMID: 36009222 PMCID: PMC9405454 DOI: 10.3390/antiox11081503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Revised: 07/18/2022] [Accepted: 07/22/2022] [Indexed: 12/10/2022] Open
Abstract
The antioxidant, anti-inflammatory and antiproliferative properties of Passiflora alata Curtis are due to the presence of polyphenols in its composition. Our previous work showed that non-obese diabetic (NOD) mice undergoing treatment with aqueous leaf extract of P. alata present reduced insulitis in the pancreas, possibly due to its anti-inflammatory properties. However, depending on the concentration and their ability to interact with other molecules, these phenolic compounds may promote oxidation reactions in some cellular components, such as proteins and lipids, thus presenting a pro-oxidant effect. The present work aimed to evaluate the in vitro effects of aqueous leaf extract of P. alata and its polyphenols (vitexin, isoorientin, rutin and catechin) on lymphocyte proliferation and viability, the cell cycle and oxidative stress. Our results showed that T lymphocytes stimulated with concanavalin A mitogen (ConA) and in the presence of IC50 concentrations of P. alata extract and polyphenols undergo cell injury via inhibition of proliferation, with these effects being more pronounced concerning CD4+ T cells (P. alata, 3.54 ± 0.34%; isoorientin, 57.07 ± 6.4%; vitexin, 16.95 ± 1.11%; catechin, 37.9 ± 4.2% and rutin, 40.14 ± 4.5%), compared to the non-treated group (77.17 ± 6.29) (p < 0.0001 for all comparisons). This process includes late apoptosis/necrosis induction (P. alata, 77.5 ± 0.7%; vitexin, 83 ± 3.3%; isoorientin, 83.8 ± 1.4%; catechin, 83 ± 1.9% and rutin, 74.9 ± 3.2, while the control presented 53.6% ± 3.1 (p < 0.0001 for all comparisons)) and mitochondrial depolarization leading to cell-death induction. Furthermore, an in vitro model of a mixed culture of NOD mice T cells with a mouse pancreatic beta-cell line (MIN6) showed increased intracellular nitric oxide and lipid peroxidation in NOD T cells submitted to P. alata extract (46.41 ± 3.08) compared to the untreated control group (33.57 ± 1.99, p = 0.01315). These results suggest that aqueous leaf extract of P. alata and the polyphenols in these leaves represent a target for translational research showing the plant’s benefits for developing new drugs with immunomodulatory properties against inflammatory diseases such as diabetes mellitus.
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30
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Hung SW, Li Y, Chen X, Chu KO, Zhao Y, Liu Y, Guo X, Man GCW, Wang CC. Green Tea Epigallocatechin-3-Gallate Regulates Autophagy in Male and Female Reproductive Cancer. Front Pharmacol 2022; 13:906746. [PMID: 35860020 PMCID: PMC9289441 DOI: 10.3389/fphar.2022.906746] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 05/17/2022] [Indexed: 11/29/2022] Open
Abstract
With a rich abundance of natural polyphenols, green tea has become one of the most popular and healthiest nonalcoholic beverages being consumed worldwide. Epigallocatechin-3-gallate (EGCG) is the predominant catechin found in green tea, which has been shown to promote numerous health benefits, including metabolic regulation, antioxidant, anti-inflammatory, and anticancer. Clinical studies have also shown the inhibitory effects of EGCG on cancers of the male and female reproductive system, including ovarian, cervical, endometrial, breast, testicular, and prostate cancers. Autophagy is a natural, self-degradation process that serves important functions in both tumor suppression and tumor cell survival. Naturally derived products have the potential to be an effective and safe alternative in balancing autophagy and maintaining homeostasis during tumor development. Although EGCG has been shown to play a critical role in the suppression of multiple cancers, its role as autophagy modulator in cancers of the male and female reproductive system remains to be fully discussed. Herein, we aim to provide an overview of the current knowledge of EGCG in targeting autophagy and its related signaling mechanism in reproductive cancers. Effects of EGCG on regulating autophagy toward reproductive cancers as a single therapy or cotreatment with other chemotherapies will be reviewed and compared. Additionally, the underlying mechanisms and crosstalk of EGCG between autophagy and other cellular processes, such as reactive oxidative stress, ER stress, angiogenesis, and apoptosis, will be summarized. The present review will help to shed light on the significance of green tea as a potential therapeutic treatment for reproductive cancers through regulating autophagy.
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Affiliation(s)
- Sze Wan Hung
- Department of Obstetrics and Gynaecology, The Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
| | - Yiran Li
- Department of Obstetrics and Gynaecology, The Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
| | - Xiaoyan Chen
- Department of Obstetrics and Gynaecology, The Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
- Department of Obstetrics and Gynaecology, Shenzhen Baoan Women’s and Children’s Hospital, Shenzhen University, Shenzhen, China
| | - Kai On Chu
- Department of Ophthalmology and Visual Sciences, Hong Kong Eye Hospital, The Chinese University of Hong Kong, Hong Kong, China
| | - Yiwei Zhao
- Department of Obstetrics and Gynaecology, The Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
- Department of Obstetrics and Gynecology, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Yingyu Liu
- Department of Obstetrics and Gynaecology, The Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
- Department of Obstetrics and Gynaecology, Shenzhen Baoan Women’s and Children’s Hospital, Shenzhen University, Shenzhen, China
| | - Xi Guo
- Department of Obstetrics and Gynaecology, The Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
| | - Gene Chi-Wai Man
- Department of Obstetrics and Gynaecology, The Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
- Department of Orthopaedics and Traumatology, The Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
- *Correspondence: Gene Chi-Wai Man, ; Chi Chiu Wang,
| | - Chi Chiu Wang
- Department of Obstetrics and Gynaecology, The Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
- Li Ka Shing Institute of Health Sciences; School of Biomedical Sciences; and Chinese University of Hong Kong-Sichuan University Joint Laboratory in Reproductive Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
- *Correspondence: Gene Chi-Wai Man, ; Chi Chiu Wang,
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31
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Mozihim AK, Chung I, Said NABM, Jamil AHA. Reprogramming of Fatty Acid Metabolism in Gynaecological Cancers: Is There a Role for Oestradiol? Metabolites 2022; 12:metabo12040350. [PMID: 35448537 PMCID: PMC9031151 DOI: 10.3390/metabo12040350] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Revised: 04/07/2022] [Accepted: 04/12/2022] [Indexed: 11/16/2022] Open
Abstract
Gynaecological cancers are among the leading causes of cancer-related death among women worldwide. Cancer cells undergo metabolic reprogramming to sustain the production of energy and macromolecules required for cell growth, division and survival. Emerging evidence has provided significant insights into the integral role of fatty acids on tumourigenesis, but the metabolic role of high endogenous oestrogen levels and increased gynaecological cancer risks, notably in obesity, is less understood. This is becoming a renewed research interest, given the recently established association between obesity and incidence of many gynaecological cancers, including breast, ovarian, cervical and endometrial cancers. This review article, hence, comprehensively discusses how FA metabolism is altered in these gynaecological cancers, highlighting the emerging role of oestradiol on the actions of key regulatory enzymes of lipid metabolism, either directly through its classical ER pathways, or indirectly via the IGIFR pathway. Given the dramatic rise in obesity and parallel increase in the prevalence of gynaecological cancers among premenopausal women, further clarifications of the complex mechanisms underpinning gynaecological cancers are needed to inform future prevention efforts. Hence, in our review, we also highlight opportunities where metabolic dependencies can be exploited as viable therapeutic targets for these hormone-responsive cancers.
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Affiliation(s)
- Azilleo Kristo Mozihim
- Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, University of Malaya, Kuala Lumpur 50603, Malaysia; (A.K.M.); (N.A.B.M.S.)
| | - Ivy Chung
- Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia;
| | - Nur Akmarina B. M. Said
- Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, University of Malaya, Kuala Lumpur 50603, Malaysia; (A.K.M.); (N.A.B.M.S.)
| | - Amira Hajirah Abd Jamil
- Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, University of Malaya, Kuala Lumpur 50603, Malaysia; (A.K.M.); (N.A.B.M.S.)
- Correspondence: ; Tel.: +60-3-7967-4909
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Khan MI, Bouyahya A, Hachlafi NEL, Menyiy NE, Akram M, Sultana S, Zengin G, Ponomareva L, Shariati MA, Ojo OA, Dall'Acqua S, Elebiyo TC. Anticancer properties of medicinal plants and their bioactive compounds against breast cancer: a review on recent investigations. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:24411-24444. [PMID: 35064485 DOI: 10.1007/s11356-021-17795-7] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Accepted: 11/23/2021] [Indexed: 05/05/2023]
Abstract
Breast cancer (BC) is one of the most common and recurring diseases and the second leading cause of death in women. Despite prevention, diagnostics, and therapeutic options such as radiation therapy and chemotherapy, the number of occurrences increases every year. Therefore, novel therapeutic drugs targeting specifically different checkpoints should be developed against breast cancer. Among drugs that can be developed to treat breast cancer, natural products, such as plant-derived compounds, showed significant anti-breast cancer properties. These substances belong to different chemical classes such as flavonoids, terpenoids, phenolic acids, and alkaloids. They exert their in vitro and in vivo cytotoxic activities against breast cancer cell lines via different mechanisms, including the inhibition of extrinsic and intrinsic apoptotic pathways, the arrest of the cell cycle, and the activation of autophagy. Moreover, they also exhibit anti-angiogenesis and antimetastatic action. Moreover, chemoprevention effects of these bioactive compounds were signaled only for certain drugs. Therefore, the aim of this review is to highlight the pharmacological actions of medicinal plants and their bioactive compounds on breast cancer. Moreover, the role of these substances in breast cancer chemoprevention was also discussed.
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Affiliation(s)
- Muhammad Idrees Khan
- Department of Eastern Medicine, Faculty of Medical Science, Government College University Faisalabad, Faisalabad, Pakistan
| | - Abdelhakim Bouyahya
- Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, Mohammed V University in Rabat, Rabat, Morocco.
| | - Naoufal E L Hachlafi
- Microbial Biotechnology and Bioactive Molecules Laboratory, Sciences and Technologies Faculty, Sidi Mohamed Ben Abdellah University, Imouzzer Road, P.O. Box-2002, Fez, Morocco
| | - Naoual El Menyiy
- Laboratory of Physiology, Faculty of Science, Faculty of Sciences Dhar El Mahraz, University Sidi Mohamed Ben Abdellah, Pharmacology & Environmental Health, Fez, Morocco
| | - Muhammad Akram
- Department of Eastern Medicine, Faculty of Medical Science, Government College University Faisalabad, Faisalabad, Pakistan
| | - Sabira Sultana
- Department of Eastern Medicine, Faculty of Medical Science, Government College University Faisalabad, Faisalabad, Pakistan
| | - Gokhan Zengin
- Biochemistry and Physiology Laboratory, Department of Biology, Faculty of Science, Selcuk University, Campus, Konya, Turkey.
| | - Lilya Ponomareva
- K.G. Razumovsky Moscow State University of Technologies and Management (the First Cossack University), 73 Zemlyanoy Val, Moscow, 109004, Russian Federation
| | - Mohammad Ali Shariati
- K.G. Razumovsky Moscow State University of Technologies and Management (the First Cossack University), 73 Zemlyanoy Val, Moscow, 109004, Russian Federation
| | | | - Stefano Dall'Acqua
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131, Padova, Italy.
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Leo M, Muccillo L, Dugo L, Bernini R, Santi L, Sabatino L. Polyphenols Extracts from Oil Production Waste Products (OPWPs) Reduce Cell Viability and Exert Anti-Inflammatory Activity via PPARγ Induction in Colorectal Cancer Cells. Antioxidants (Basel) 2022; 11:antiox11040624. [PMID: 35453308 PMCID: PMC9029425 DOI: 10.3390/antiox11040624] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 03/11/2022] [Accepted: 03/21/2022] [Indexed: 02/07/2023] Open
Abstract
Olive oil production is associated with the generation of oil production waste products (OPWPs) rich in water-soluble polyphenols that represent serious environmental problems. Yet OPWPs can offer new opportunities by exploiting their bioactive properties. In this study, we chemically characterized OPWPs polyphenolic extracts and investigated their biological activities in normal and colorectal cancer cells. Hydroxytyrosol (HTyr), the major constituent of these extracts, was used as the control. We show that both HTyr and the extracts affect cell viability by inducing apoptosis and cell cycle arrest. They downregulate inflammation by impairing NF-κB phosphorylation and expression of responsive cytokine genes, as TNF-α and IL-8, at both mRNA and protein levels, and prevent any further increase elicited by external challenges. Mechanistically, HTyr and the extracts activate PPARγ while hampering pro-inflammatory genes expression, acting as a specific agonist, likely through a trans-repression process. Altogether, OPWPs polyphenolic extracts show stronger effects than HTyr, conceivably due to additive or synergistic effects of all polyphenols contained. They display anti-inflammatory properties and these results may pave the way for improving OPWPs extraction and enrichment methods to reduce the environmental impact and support their use to ameliorate the inflammation associated with diseases and tumors.
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Affiliation(s)
- Manuela Leo
- Department of Sciences and Technologies, University of Sannio, Via F. De Sanctis, 82100 Benevento, Italy; (M.L.); (L.M.)
| | - Livio Muccillo
- Department of Sciences and Technologies, University of Sannio, Via F. De Sanctis, 82100 Benevento, Italy; (M.L.); (L.M.)
| | - Laura Dugo
- Department of Science and Technology for Humans and the Environment, University Campus Bio-Medico of Rome, Via Alvaro del Portillo 21, 00128 Roma, Italy;
| | - Roberta Bernini
- Department of Agriculture and Forest Sciences, University of Tuscia, Via San Camillo de Lellis snc, 01100 Viterbo, Italy; (R.B.); (L.S.)
| | - Luca Santi
- Department of Agriculture and Forest Sciences, University of Tuscia, Via San Camillo de Lellis snc, 01100 Viterbo, Italy; (R.B.); (L.S.)
| | - Lina Sabatino
- Department of Sciences and Technologies, University of Sannio, Via F. De Sanctis, 82100 Benevento, Italy; (M.L.); (L.M.)
- Correspondence: ; Tel.: +39-0824-305149 or +39-0824-305167
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Singla RK, Sharma P, Dubey AK, Gundamaraju R, Kumar D, Kumar S, Madaan R, Shri R, Tsagkaris C, Parisi S, Joon S, Singla S, Kamal MA, Shen B. Natural Product-Based Studies for the Management of Castration-Resistant Prostate Cancer: Computational to Clinical Studies. Front Pharmacol 2021; 12:732266. [PMID: 34737700 PMCID: PMC8560712 DOI: 10.3389/fphar.2021.732266] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 09/06/2021] [Indexed: 02/05/2023] Open
Abstract
Background: With prostate cancer being the fifth-greatest cause of cancer mortality in 2020, there is a dire need to expand the available treatment options. Castration-resistant prostate cancer (CRPC) progresses despite androgen depletion therapy. The mechanisms of resistance are yet to be fully discovered. However, it is hypothesized that androgens depletion enables androgen-independent cells to proliferate and recolonize the tumor. Objectives: Natural bioactive compounds from edible plants and herbal remedies might potentially address this need. This review compiles the available cheminformatics-based studies and the translational studies regarding the use of natural products to manage CRPC. Methods: PubMed and Google Scholar searches for preclinical studies were performed, while ClinicalTrials.gov and PubMed were searched for clinical updates. Studies that were not in English and not available as full text were excluded. The period of literature covered was from 1985 to the present. Results and Conclusion: Our analysis suggested that natural compounds exert beneficial effects due to their broad-spectrum molecular disease-associated targets. In vitro and in vivo studies revealed several bioactive compounds, including rutaecarpine, berberine, curcumin, other flavonoids, pentacyclic triterpenoids, and steroid-based phytochemicals. Molecular modeling tools, including machine and deep learning, have made the analysis more comprehensive. Preclinical and clinical studies on resveratrol, soy isoflavone, lycopene, quercetin, and gossypol have further validated the translational potential of the natural products in the management of prostate cancer.
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Affiliation(s)
- Rajeev K. Singla
- Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
- iGlobal Research and Publishing Foundation, New Delhi, India
| | - Pooja Sharma
- Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India
- Khalsa College of Pharmacy, Amritsar, India
| | | | - Rohit Gundamaraju
- ER Stress and Mucosal Immunology Lab, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia
| | - Dinesh Kumar
- Department of Pharmaceutical Sciences, Sri Sai College of Pharmacy, Amritsar, India
| | - Suresh Kumar
- Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India
| | - Reecha Madaan
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Richa Shri
- Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India
| | | | - Salvatore Parisi
- Lourdes Matha Institute of Hotel Management and Catering Technology, Thiruvananthapuram, India
| | - Shikha Joon
- Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
- iGlobal Research and Publishing Foundation, New Delhi, India
| | - Shailja Singla
- iGlobal Research and Publishing Foundation, New Delhi, India
| | - Mohammad Amjad Kamal
- West China School of Nursing/Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
- King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
- Enzymoics; Novel Global Community Educational Foundation, Hebersham, NSW, Australia
| | - Bairong Shen
- Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
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Costa R, Costa Lima SA, Gameiro P, Reis S. On the Development of a Cutaneous Flavonoid Delivery System: Advances and Limitations. Antioxidants (Basel) 2021; 10:1376. [PMID: 34573007 PMCID: PMC8472229 DOI: 10.3390/antiox10091376] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 08/09/2021] [Accepted: 08/19/2021] [Indexed: 12/11/2022] Open
Abstract
Flavonoids are one of the vital classes of natural polyphenolic compounds abundantly found in plants. Due to their wide range of therapeutic properties, which include antioxidant, anti-inflammatory, photoprotective, and depigmentation effects, flavonoids have been demonstrated to be promising agents in the treatment of several skin disorders. However, their lipophilic nature and poor water solubility invariably lead to limited oral bioavailability. In addition, they are rapidly degraded and metabolized in the human body, hindering their potential contribution to the prevention and treatment of many disorders. Thus, to overcome these challenges, several cutaneous delivery systems have been extensively studied. Topical drug delivery besides offering an alternative administration route also ensures a sustained release of the active compound at the desired site of action. Incorporation into lipid or polymer-based nanoparticles appears to be a highly effective approach for cutaneous delivery of flavonoids with good encapsulation potential and reduced toxicity. This review focuses on currently available formulations used to administer either topically or systemically different classes of flavonoids in the skin, highlighting their potential application as therapeutic and preventive agents.
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Affiliation(s)
- Raquel Costa
- LAQV, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal; (R.C.); (S.A.C.L.)
- LAQV, REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, 4169-007 Porto, Portugal;
| | - Sofia A. Costa Lima
- LAQV, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal; (R.C.); (S.A.C.L.)
| | - Paula Gameiro
- LAQV, REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, 4169-007 Porto, Portugal;
| | - Salette Reis
- LAQV, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal; (R.C.); (S.A.C.L.)
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Romano A, Martel F. The Role of EGCG in Breast Cancer Prevention and Therapy. Mini Rev Med Chem 2021; 21:883-898. [PMID: 33319659 DOI: 10.2174/1389557520999201211194445] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 09/02/2020] [Accepted: 09/05/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Breast cancer is the most frequent cancer in women. Green tea has been studied for breast cancer chemopreventive and possibly chemotherapeutic effects due to its high content in polyphenolic compounds, including epigallocatechin-3-gallate (EGCG). METHOD This review is based on literature research that included papers registered on the Medline® database. The research was conducted through PubMed, applying the following query: "EGCG"AND "breast cancer". The result was a total of 88 articles in which this review stands on. RESULTS In vitro, EGCG shows antioxidant or pro-oxidant properties, depending on the concentration and exposure time. EGCG blocks cell cycle progression and modulates signaling pathways that affect cell proliferation and differentiation. EGCG also induces apoptosis, negatively modulates different steps involved in metastasis, and targets angiogenesis by inhibiting VEGF transcription. In vivo investigations have shown that oral administration of EGCG results in the reduction of tumor growth and in antimetastatic and antiangiogenic effects in animal xenograft and allograft models. DISCUSSION Much remains unknown about the molecular mechanisms involved in the protective effects of EGCG on mammary carcinogenesis. In addition, more studies in vivo are necessary to determine the potential toxicity of EGCG at higher doses and to elucidate its interactions with other drugs. CONCLUSION A protective effect of EGCG has been shown in different experimental models and under different experimental conditions, suggesting clinical implications of EGCG for breast cancer prevention and therapy. The data presented in this review support the importance of further investigations.
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Affiliation(s)
- Adriana Romano
- Faculty of Medicine of University of Porto, Porto, Portugal
| | - Fátima Martel
- Department of Biomedicine-Unit of Biochemistry, Faculty of Medicine of University of Porto, Porto, Portugal and Instituto de Investigacao e Inovacao em Saude(i3S), University of Porto, Porto, Portugal
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Chandra G, Patel S, Panchal M, Singh DV. S-adenosyl-L-homocysteine Hydrolase: Its Inhibitory Activity Against Plasmodium falciparum and Development of Malaria Drugs. Mini Rev Med Chem 2021; 21:833-846. [PMID: 33342411 DOI: 10.2174/1389557521666201218155321] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 10/31/2020] [Accepted: 11/02/2020] [Indexed: 11/22/2022]
Abstract
Parasite Plasmodium falciparum is continuously giving a challenge to human beings by changing itself against most of the antimalarial drugs and its consequences can be seen in the form of a huge number of deaths each year especially in the poor and developing country. Due to its drug resistance ability, new drugs are regularly needed to kill the organism. Many new drugs have been developed based on different mechanisms. One of the potential mechanisms is to hamper protein synthesis by blocking the gene expression. S-Adenosyl-L-homocysteine (SAH) hydrolase is a NAD+ dependent tetrameric enzyme, which is responsible for the reversible hydrolysis of AdoHcy to adenosine and L-homocysteine, has been recognized as a new target for antimalarial agents since the parasite has a specific SAH hydrolase. The inhibition of SAH hydrolase causes the intracellular accumulation of S-Adenosyl-L-homocysteine, elevating the ratio of SAH to S-adenosylmethionine (SAM) and inhibiting SAM-dependent methyltransferase that catalyzes methylation of the capped structure at the 5'-terminus of mRNA, and other methylation reaction which is essential for parasite proliferation. In other words, S-Adenosyl-Lhomocysteine hydrolase regulates methyltransferase reactions. In this way, SAH hydrolase inhibitors can be used for the treatment of different diseases like malaria, cancer, viral infection, etc. by ultimately stopping the synthesis of protein. Many antiviral drugs have been synthesized and marketed which are based on the inhibition of SAH hydrolase. This review summarises the development of SAH inhibitors developed over the last 20 years and their potentiality for the treatment of malaria.
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Affiliation(s)
- Girish Chandra
- Department of Chemistry, School of Physical and Chemical Sciences, Central University of South Bihar, Gaya, Bihar, India
| | - Samridhi Patel
- Department of Chemistry, School of Physical and Chemical Sciences, Central University of South Bihar, Gaya, Bihar, India
| | - Manoj Panchal
- Department of Life Science, School of Earth, Biological and Environmental Science, Central University of South Bihar, Gaya, Bihar, India
| | - Durg Vijay Singh
- Department of Bioinformatics, School of Earth, Biological and Environmental Science, Central University of South Bihar, Gaya, Bihar, India
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Upreti S, Pandey SC, Bisht I, Samant M. Evaluation of the target-specific therapeutic potential of herbal compounds for the treatment of cancer. Mol Divers 2021; 26:1823-1835. [PMID: 34240331 DOI: 10.1007/s11030-021-10271-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Accepted: 07/02/2021] [Indexed: 11/25/2022]
Abstract
Cancer is among one of the most fatal diseases leading to millions of death around the globe. Chemotherapy is the most popular conventional approach for the treatment of cancer. However, this is usually associated with various side effects and puts the patients under extreme physical and mental stress. Besides, there are increasing concerns about drug resistance. Thus, to surmount these limitations, there is a need to explore some alternative treatments. Studies related to plant-derived compounds are crucial in the search for safer and more efficient treatments. Plants and their associated secondary metabolites have been a revolutionary approach in the field of cancer treatment, as they give answers to almost all the constraints faced by synthetic drugs. Various plants and associated secondary metabolites display a great prospective as cytotoxic anticancer agents due to their specific interference with validated drug targets, such as inhibitors of mitosis, topoisomerase I and II inhibitor, DNA interactive agent, protein kinase inhibitors, inhibitors of DNA synthesis. In this review, the therapeutic potential of various natural compounds and their derivatives are presented based on their molecular targets. These herbal compounds and their derivatives could provide a rich resource for novel anticancer drug development.
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Affiliation(s)
- Shobha Upreti
- Cell and Molecular Biology Laboratory, Department Of Zoology, Kumaun University, SSJ Campus, Almora, Uttarakhand, India
| | - Satish Chandra Pandey
- Cell and Molecular Biology Laboratory, Department Of Zoology, Kumaun University, SSJ Campus, Almora, Uttarakhand, India
| | - Ila Bisht
- Cell and Molecular Biology Laboratory, Department Of Zoology, Kumaun University, SSJ Campus, Almora, Uttarakhand, India
| | - Mukesh Samant
- Cell and Molecular Biology Laboratory, Department Of Zoology, Kumaun University, SSJ Campus, Almora, Uttarakhand, India.
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Ling YTQ, Heng YX, Chan HH, Yap YJ, Lee SY, Koh RY, Liew YK, Manaf SNQ, Ang DTC, Mok KL. Evaluation of biocompatible palm-based polymeric surfactants for potential natural rubber latex stabilisation applications. J RUBBER RES 2021. [DOI: 10.1007/s42464-021-00104-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Patra S, Nayak R, Patro S, Pradhan B, Sahu B, Behera C, Bhutia SK, Jena M. Chemical diversity of dietary phytochemicals and their mode of chemoprevention. BIOTECHNOLOGY REPORTS (AMSTERDAM, NETHERLANDS) 2021; 30:e00633. [PMID: 34094892 PMCID: PMC8167155 DOI: 10.1016/j.btre.2021.e00633] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 05/16/2021] [Accepted: 05/17/2021] [Indexed: 12/24/2022]
Abstract
Despite the advancement in prognosis, diagnosis and treatment, cancer has emerged as the second leading cause of disease-associated death across the globe. With the remarkable application of synthetic drugs in cancer therapy and the onset of therapy-associated adverse effects, dietary phytochemicals have been materialized as potent anti-cancer drugs owing to their antioxidant, apoptosis and autophagy modulating activities. With dynamic regulation of apoptosis and autophagy in association with cell cycle regulation, inhibition in cellular proliferation, invasion and migration, dietary phytochemicals have emerged as potent anti-cancer pharmacophores. Dietary phytochemicals or their synthetic analogous as individual drug candidates or in combination with FDA approved chemotherapeutic drugs have exhibited potent anti-cancer efficacy. With the advancement in cancer therapeutics, dietary phytochemicals hold high prevalence for their use as precision and personalized medicine to replace conventional chemotherapeutic drugs. Hence, keeping these perspectives in mind, this review focuses on the diversity of dietary phytochemicals and their molecular mechanism of action in several cancer subtypes and tumor entities. Understanding the possible molecular key players involved, the use of dietary phytochemicals will thrive a new horizon in cancer therapy.
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Affiliation(s)
- Srimanta Patra
- Cancer and Cell Death Laboratory, Department of Life Science, National Institute of Technology Rourkela, India
| | - Rabindra Nayak
- Post Graduate Department of Botany, Berhampur University, Bhanja Bihar, Berhampur, 760007, India
| | - Suryamani Patro
- Department of Home Science, S.B.R. Govt. Women’s College, Berhampur, 760001, India
| | - Biswajita Pradhan
- Post Graduate Department of Botany, Berhampur University, Bhanja Bihar, Berhampur, 760007, India
| | | | - Chhandashree Behera
- Post Graduate Department of Botany, Berhampur University, Bhanja Bihar, Berhampur, 760007, India
| | - Sujit Kumar Bhutia
- Cancer and Cell Death Laboratory, Department of Life Science, National Institute of Technology Rourkela, India
| | - Mrutyunjay Jena
- Post Graduate Department of Botany, Berhampur University, Bhanja Bihar, Berhampur, 760007, India
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Jiang Y, Jiang Z, Ma L, Huang Q. Advances in Nanodelivery of Green Tea Catechins to Enhance the Anticancer Activity. Molecules 2021; 26:3301. [PMID: 34072700 PMCID: PMC8198522 DOI: 10.3390/molecules26113301] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 05/25/2021] [Accepted: 05/25/2021] [Indexed: 12/12/2022] Open
Abstract
Cancer is one of the leading causes of death globally. A variety of phenolic compounds display preventative and therapeutic effects against cancers. Green teas are rich in phenolics. Catechins are the most dominant phenolic component in green teas. Studies have shown that catechins have anticancer activity in various cancer models. The anticancer activity of catechins, however, may be compromised due to their low oral bioavailability. Nanodelivery emerges as a promising way to improve the oral bioavailability and anticancer activity of catechins. Research in this area has been actively conducted in recent decades. This review provides the molecular mechanisms of the anticancer effects of catechins, the factors that limit the oral bioavailability of catechins, and the latest advances of delivering catechins using nanodelivery systems through different routes to enhance their anticancer activity.
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Affiliation(s)
- Yike Jiang
- Shenzhen Bay Laboratory, Institute of Biomedical Health Technology and Engineering, Shenzhen 518132, China;
| | - Ziyi Jiang
- Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China;
- State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China
| | - Lan Ma
- Shenzhen Bay Laboratory, Institute of Biomedical Health Technology and Engineering, Shenzhen 518132, China;
- Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China;
- State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China
| | - Qingrong Huang
- Department of Food Science, Rutgers University, 65 Dudley Road, New Brunswick, NJ 08901, USA
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Systematic integrated analyses of methylomic and transcriptomic impacts of early combined botanicals on estrogen receptor-negative mammary cancer. Sci Rep 2021; 11:9481. [PMID: 33947955 PMCID: PMC8096837 DOI: 10.1038/s41598-021-89131-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 04/21/2021] [Indexed: 11/09/2022] Open
Abstract
Dietary botanicals such as the cruciferous vegetable broccoli sprouts (BSp) as well as green tea polyphenols (GTPs) have shown exciting potential in preventing or delaying breast cancer (BC). However, little is known about their impact on epigenomic aberrations that are centrally involved in the initiation and progression of estrogen receptor-negative [ER(−)] BC. We have investigated the efficacy of combined BSp and GTPs diets on mammary tumor inhibition in transgenic Her2/neu mice that were administered the diets from prepubescence until adulthood. Herein, we present an integrated DNA methylome and transcriptome analyses for defining the early-life epigenetic impacts of combined BSp and GTPs on mammary tumors and our results indicate that a combinatorial administration of BSp and GTPs have a stronger impact at both transcriptome and methylome levels in comparison to BSp or GTPs administered alone. We also demonstrated a streamlined approach by performing an extensive preprocessing, quality assessment and downstream analyses on the genomic dataset. Our identification of differentially methylated regions in response to dietary botanicals administered during early-life will allow us to identify key genes and facilitate implementation of the subsequent downstream functional analyses on a genomic scale and various epigenetic modifications that are crucial in preventing ER(−) mammary cancer. Furthermore, our realtime PCR results were also found to be consistent with our genome-wide analysis results. These results could be exploited as a comprehensive resource for understanding understudied genes and their associated epigenetic modifications in response to these dietary botanicals.
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Das A, Haque I, Ray P, Ghosh A, Dutta D, Quadir M, De A, Gunewardena S, Chatterjee I, Banerjee S, Weir S, Banerjee SK. CCN5 activation by free or encapsulated EGCG is required to render triple-negative breast cancer cell viability and tumor progression. Pharmacol Res Perspect 2021; 9:e00753. [PMID: 33745223 PMCID: PMC7981588 DOI: 10.1002/prp2.753] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Revised: 02/13/2021] [Accepted: 02/15/2021] [Indexed: 12/11/2022] Open
Abstract
Epigallocatechin-3-gallate (EGCG) has been considered an anticancer agent despite conflicting and discrepant bioavailability views. EGCG impairs the viability and self-renewal capacity of triple-negative breast cancer (TNBC) cells and makes them sensitive to estrogen via activating ER-α. Surprisingly, the mechanism of EGCG's action on TNBC cells remains unclear. CCN5/WISP-2 is a gatekeeper gene that regulates viability, ER-α, and stemness in TNBC and other types of cancers. This study aimed to investigate whether EGCG (free or encapsulated in nanoparticles) interacts with the CCN5 protein by emphasizing its bioavailability and enhancing its anticancer effect. We demonstrate that EGCG activates CCN5 to inhibit in vitro cell viability through apoptosis, the sphere-forming ability via reversing TNBC cells' stemness, and suppressing tumor growth in vivo. Moreover, we found EGCG-loaded nanoparticles to be functionally more active and superior in their tumor-suppressing ability than free-EGCG. Together, these studies identify EGCG (free or encapsulated) as a novel activator of CCN5 in TNBC cells and hold promise as a future therapeutic option for TNBC with upregulated CCN5 expression.
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Affiliation(s)
- Amlan Das
- Cancer Research UnitVA Medical CenterKansas CityMOUSA
- Present address:
National Institute of Biomedical GenomicsKalyaniWest BengalIndia
| | - Inamul Haque
- Cancer Research UnitVA Medical CenterKansas CityMOUSA
| | - Priyanka Ray
- Department of Chemical Biochemical Environmental Engineering (CBEEUniversity of MarylandBaltimoreMDUSA
| | - Arnab Ghosh
- Cancer Research UnitVA Medical CenterKansas CityMOUSA
- Department of Pathology and Laboratory MedicineUniversity of Kansas Medical CenterKansas CityKSUSA
| | - Debasmita Dutta
- Department of Coatings and Polymeric MaterialsNorth Dakota State UniversityFargoNDUSA
| | - Mohiuddin Quadir
- Department of Coatings and Polymeric MaterialsNorth Dakota State UniversityFargoNDUSA
| | - Archana De
- Cancer Research UnitVA Medical CenterKansas CityMOUSA
| | - Sumedha Gunewardena
- Department of Molecular and Integrative PhysiologyUniversity of Kansas Medical CenterKansas CityKSUSA
| | - Indranil Chatterjee
- Cancer Research UnitVA Medical CenterKansas CityMOUSA
- Present address:
Department of Life SciencesCentral University of Tamil NaduThiruvarurIndia
| | - Snigdha Banerjee
- Cancer Research UnitVA Medical CenterKansas CityMOUSA
- Department of Pathology and Laboratory MedicineUniversity of Kansas Medical CenterKansas CityKSUSA
| | - Scott Weir
- Department of PharmacologyToxicology and TherapeuticsUniversity of Kansas Medical CenterKansas CityKSUSA
| | - Sushanta K. Banerjee
- Cancer Research UnitVA Medical CenterKansas CityMOUSA
- Department of Pathology and Laboratory MedicineUniversity of Kansas Medical CenterKansas CityKSUSA
- Lead contact, SKB, Cancer Research UnitKansas CityMOUSA
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Patra S, Pradhan B, Nayak R, Behera C, Panda KC, Das S, Jena M, Bhutia SK. Apoptosis and autophagy modulating dietary phytochemicals in cancer therapeutics: Current evidences and future perspectives. Phytother Res 2021; 35:4194-4214. [DOI: 10.1002/ptr.7082] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2020] [Revised: 02/25/2021] [Accepted: 02/25/2021] [Indexed: 12/12/2022]
Affiliation(s)
- Srimanta Patra
- Cancer and Cell Death Laboratory, Department of Life Science National Institute of Technology Rourkela Rourkela Odisha India
| | - Biswajita Pradhan
- Post Graduate Department of Botany Berhampur University Berhampur Odisha India
| | - Rabindra Nayak
- Post Graduate Department of Botany Berhampur University Berhampur Odisha India
| | - Chhandashree Behera
- Post Graduate Department of Botany Berhampur University Berhampur Odisha India
| | - Krishna Chandra Panda
- Department of Pharmaceutical Chemistry Roland Institute of Pharmaceutical Sciences Berhampur Odisha India
| | - Surajit Das
- Laboratory of Environmental Microbiology and Ecology, Department of Life Science National Institute of Technology Rourkela Rourkela Odisha India
| | - Mrutyunjay Jena
- Post Graduate Department of Botany Berhampur University Berhampur Odisha India
| | - Sujit Kumar Bhutia
- Cancer and Cell Death Laboratory, Department of Life Science National Institute of Technology Rourkela Rourkela Odisha India
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Proliferation of MDA-MB-231 can be suppressed by dimeric-epigallocatechin gallate through competitive inhibition of amphiregulin-epidermal growth factor receptor signaling. Anticancer Drugs 2021; 32:647-656. [PMID: 33587351 DOI: 10.1097/cad.0000000000001038] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Triple-negative breast cancer (TNBC) is highly aggressive, with high rates of early relapse and very poor overall prognosis. Amphiregulin (AREG) is the most abundant epidermal growth factor receptor (EGFR) agonist in MDA-MB-231 TNBC cells, whose proliferation can be inhibited by (-)-epigallocatechin gallate (EGCG), a constituent of green tea that is prone to oxidative polymerization. The effect of dimeric-EGCG, a dimer of oxidized and polymerized EGCG, on MDA-MB-231 cell the proliferation warrants further exploration. In the present study, MTT, flow cytometry, migration scratch, transwell, western blotting, and surface plasmon resonance assays were used to evaluate the effect of dimeric-EGCG on MDA-MB-231 cells and explore the underlying mechanism. MDA-MB-231 cell proliferation and migration were significantly inhibited by dimeric-EGCG at concentrations as low as 10 μM. Levels of EGFR and p44/42 MAPK phosphorylation in MDA-MB-231 cells were significantly reduced by treatment with 10 μM dimeric-EGCG (P < 0.01). In addition, the levels of phosphorylation induced by exogenous AREG were also inhibited by dimeric-EGCG (P < 0.01); however, no significant effects of dimeric-EGCG were observed on epidermal growth factor or transforming growth factor-alpha signaling. Surface plasmon resonance analysis demonstrated that 10 μM dimeric-EGCG bound directly to the extracellular domain of EGFR, competitively inhibiting the binding of AREG to EGFR. These results suggest a novel mechanism underlying the inhibitory effect of dimeric-EGCG on MDA-MB-231 cells, with potential application in the development of drugs for the treatment of TNBC.
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Green Tea Catechins Induce Inhibition of PTP1B Phosphatase in Breast Cancer Cells with Potent Anti-Cancer Properties: In Vitro Assay, Molecular Docking, and Dynamics Studies. Antioxidants (Basel) 2020; 9:antiox9121208. [PMID: 33266280 PMCID: PMC7761018 DOI: 10.3390/antiox9121208] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 11/12/2020] [Accepted: 11/24/2020] [Indexed: 12/16/2022] Open
Abstract
The catechins derived from green tea possess antioxidant activity and may have a potentially anticancer effect. PTP1B is tyrosine phosphatase that is oxidative stress regulated and is involved with prooncogenic pathways leading to the formation of a.o. breast cancer. Here, we present the effect of selected green tea catechins on enzymatic activity of PTP1B phosphatase and viability of MCF-7 breast cancer cells. We showed also the computational analysis of the most effective catechin binding with a PTP1B molecule. We observed that epigallocatechin, epigallocatechin gallate, epicatechin, and epicatechin gallate may decrease enzymatic activity of PTP1B phosphatase and viability of MCF-7 cells. Conclusions: From the tested compounds, epigallocatechin and epigallocatechin gallate were the most effective inhibitors of the MCF-7 cell viability. Moreover, epigallocatechin was also the strongest inhibitor of PTP1B activity. Computational analysis allows us also to conclude that epigallocatechin is able to interact and bind to PTP1B. Our results suggest also the most predicted binding site to epigallocatechin binding to PTP1B.
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Changizi V, Azariasl S, Motevaseli E, Jafari Nodooshan S. Assessment Synergistic Effects of Integrated Therapy with Epigallocatechin-3-Gallate (EGCG) & Arsenic Trioxide and Irradiation on Breast Cancer Cell Line. IRANIAN JOURNAL OF PUBLIC HEALTH 2020; 49:1555-1563. [PMID: 33083333 PMCID: PMC7554386 DOI: 10.18502/ijph.v49i8.3901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
Abstract
Background: Breast cancer is the most common invasive malignancy among women in the world. The current breast cancer therapies pose significant clinical challenges. Low-dose chemotherapy represents a new strategy to treat solid tumors in combination with natural products such as green tea catechins. Epigallocatechin-3-gallate (EGCG) is the major polyphenolic extract from green tea with potent anticancer and antioxidant effects. The purpose of this study was to investigate the effects of EGCG, Arsenic trioxide (ATO) and gamma radiation on MCF-7 cell line. Methods: The anti-proliferative effects of EGCG and ATO individually, moreover in combination with radiation on MCF-7 cells were evaluated with MTT assay. The expression of apoptotic gens (Bax, Bcl-2, Caspase-3 and Fas) was assessed by real-time PCR. Results: Based on the results of MTT assay, EGCG and ATO exhibited dose and time-dependent anti-proliferative effects on MCF-7 cells. The combined therapy of EGCG and ATO in presence and absence radiation could rise cell death up to 80%. Moreover, integrated therapy made Bax up-regulated and Bcl-2 down- regulated. Conclusion: In assessment synergistic effects of integrated therapy with EGCG and ATO and irradiation had been significant impact on low dose chemotherapy for breast cancer treatment.
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Affiliation(s)
- Vahid Changizi
- Department of Technology of Radiology and Radiotherapy, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
| | - Samayeh Azariasl
- Department of Technology of Radiology and Radiotherapy, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
| | - Elahe Motevaseli
- Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Saeedeh Jafari Nodooshan
- School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
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Huang X, Li J, Li M, Huang J, Jiang X, Fu H, Wu J, Bao M, Wang S, Zhang M, Gao G. Polyphenol-Enriched Extracts from Trapa acornis Husks Inhibit Her2-Positive SK-BR-3 Breast Cancer Cell Proliferation and In Vivo Tumor Angiogenesis. Nutr Cancer 2020; 73:1145-1156. [PMID: 32672134 DOI: 10.1080/01635581.2020.1792951] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
The study aimed to investigate the antitumor effects of Trapa acornis husks (TAH) extract on SK-BR-3 cells of Her2-positive breast cancer. The bioactive compounds of TAH extracts were analyzed qualitatively and quantitatively by Ultra-Performance Liquid Chromatography/Mass Spectrometry (UPLC-MS)/high-performance liquid chromatographic system (HPLC). The effects of TAH extracts on cell proliferation, cell cycle, and apoptosis of SK-BR-3 cells were determined by CCK-8 and flow cytometry. Besides, the In Vivo antitumor effect of TAH extracts was detected. UPLC-MS/HPLC showed that the main bioactive compounds of TAH were gallic acid and galloylglucose derivatives. TAH extracts significantly inhibited the proliferation of SK-BR-3 cells in a dose- and time-dependent manner (P < 0.01). With the increase of TAH extracts concentration, cells in G2/M stage were increased and cell apoptosis was significantly increased. Immunohistochemical analysis showed that TAH extracts can significantly reduce the positive expression rate of Ki67 and Factor VIII index in tumor tissues. The mRNA expression levels of VEGF, MMP2, MMP9, and uPA were reduced after TAH extracts intervention (P < 0.01). TAH extracts also decreased the protein expression of p-Her2, p-ERK1/2, VEGF, MMP2, MMP9, and uPA (P < 0.01). In conclusion, polyphenol-enriched extracts from TAH might inhibit breast cancer cell proliferation and In Vivo tumor angiogenesis.
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Affiliation(s)
- Xuan Huang
- Key Laboratory of Natural Medicine and Health Food R & D Technology, College of Medicine, Jiaxing University, Jiaxing, Zhejiang, PR China
| | - Jun Li
- Jiaxing Vocational Technical College, Jiaxing, Zhejiang, PR China
| | - Mingjuan Li
- Key Laboratory of Natural Medicine and Health Food R & D Technology, College of Medicine, Jiaxing University, Jiaxing, Zhejiang, PR China
| | - Jia Huang
- Key Laboratory of Natural Medicine and Health Food R & D Technology, College of Medicine, Jiaxing University, Jiaxing, Zhejiang, PR China
| | - Xiaohong Jiang
- Key Laboratory of Natural Medicine and Health Food R & D Technology, College of Medicine, Jiaxing University, Jiaxing, Zhejiang, PR China
| | - Hongfei Fu
- College of Food Science and Engineering, Northwest A&F University, Yangling, Shanxi, PR China
| | - Jiming Wu
- Key Laboratory of Natural Medicine and Health Food R & D Technology, College of Medicine, Jiaxing University, Jiaxing, Zhejiang, PR China
| | - Mingyang Bao
- College of Medicine, Jiaxing University, Jiaxing, Zhejiang, PR China
| | - Shuzhen Wang
- College of Medicine, Jiaxing University, Jiaxing, Zhejiang, PR China
| | - Muyuan Zhang
- College of Medicine, Jiaxing University, Jiaxing, Zhejiang, PR China
| | - Guangchun Gao
- Key Laboratory of Natural Medicine and Health Food R & D Technology, College of Medicine, Jiaxing University, Jiaxing, Zhejiang, PR China
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49
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Laganà P, Coniglio MA, Fiorino M, Delgado AM, Chammen N, Issaoui M, Gambuzza ME, Iommi C, Soraci L, Haddad MA, Delia S. Phenolic Substances in Foods and Anticarcinogenic Properties: A Public Health Perspective. J AOAC Int 2020; 103:935-939. [PMID: 33241352 DOI: 10.1093/jaocint/qsz028] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Revised: 11/04/2019] [Accepted: 11/06/2019] [Indexed: 01/23/2023]
Abstract
The interest in polyphenols from vegetable sources has been progressively increased because of the demonstrated correlation between their abundance in certain foods or food preparations of traditional importance and heritage, and the answer of anti-inflammatory strategies in hospitalized patients in the presence of polypehnol-rich foods (as a complementary therapy). Consequently, research involving the accessory role of polyphenols as anti-tumoral aids have been carried out with the aim of finding new additional strategies. The purpose of this paper to evaluate the role of phenolic compounds in foods with reference to health effects for human beings. The importance of these molecules has been evaluated by the health and safety perspectives in terms of: fight to cardiovascular diseases; prevention of chronic-degenerative disorders; general antioxidant properties; and anticarcinogenic features. Moreover, the role of polyphenols-rich foods as anticancer agents has been discussed with relation to two distinct "action plans" on the public hygiene level: the promotion of human health on the one side (for non-hospitalized and normal subjects), and reliable contrasting strategies in cancer patients.
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Affiliation(s)
- Pasqualina Laganà
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy
| | | | | | - Amélia Martins Delgado
- MeditBio-Centre for Mediterranean Bioresources and Food, University of Algarve, Faro, Portugal
| | - Nadia Chammen
- Laboratoire d'Ecologie et de Technologie Microbienne, Institut National des Sciences Appliquées et de Technologie (INSAT), University of Carthage, Tunis, Tunisia
| | - Manel Issaoui
- Lab -NAFS Nutrition - Functional Food & Vascular Health, Faculty of Medicine, University of Monastir, Monastir, Tunisia
| | - Maria E Gambuzza
- Ministry of Health, Territorial Office of Messina, Messina, Italy
| | | | - Luca Soraci
- Clinical and Experimental Medicine Department, University of Messina, Messina, Italy
| | - Moawiya A Haddad
- Department of Nutrition and Food Processing, Faculty of Agricultural Technology, Al-Balqa Applied University, Al-Salt, Jordan
| | - Santi Delia
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy
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50
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Ciebiera M, Ali M, Prince L, Jackson-Bey T, Atabiekov I, Zgliczyński S, Al-Hendy A. The Evolving Role of Natural Compounds in the Medical Treatment of Uterine Fibroids. J Clin Med 2020; 9:E1479. [PMID: 32423112 PMCID: PMC7290481 DOI: 10.3390/jcm9051479] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 05/11/2020] [Accepted: 05/11/2020] [Indexed: 12/15/2022] Open
Abstract
Uterine fibroids (UFs) remain a significant health issue for many women, with a disproportionate impact on women of color, likely due to both genetic and environmental factors. The prevalence of UFs is estimated to be approximately 70% depending on population. UF-derived clinical symptoms include pelvic pain, excessive uterine bleeding, gastrointestinal and voiding problems, as well as impaired fertility. Nowadays numerous methods of UF treatment are available-from conservative treatment to invasive surgeries. Selecting an appropriate treatment option should be individualized and adjusted to the patient's expectations as much as possible. So far, the mainstay of treatment is surgery, but their negative impact of future fertility is clear. On the other hand, emerging new pharmaceutical options have significant adverse effects like liver function impairment, hot flashes, bone density loss, endometrial changes, and inability to attempt conception during treatment. Several natural compounds are found to help treat UFs and relieve their symptoms. In this review we summarize all the current available data about natural compounds that may be beneficial for patients with UFs, especially those who want to preserve their future fertility or have treatment while actively pursuing conception. Vitamin D, epigallocatechin gallate, berberine, curcumin, and others are being used as alternative UF treatments. Moreover, we propose the concept of using combined therapies of natural compounds on their own or combined with hormonal agents to manage UFs. There is a strong need for more human clinical trials involving these compounds before promoting widespread usage.
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Affiliation(s)
- Michał Ciebiera
- Second Department of Obstetrics and Gynecology, The Center of Postgraduate Medical Education, 01-809 Warsaw, Poland;
- Department of Surgery, University of Illinois at Chicago, Chicago, IL 60612, USA;
| | - Mohamed Ali
- Department of Surgery, University of Illinois at Chicago, Chicago, IL 60612, USA;
- Clinical Pharmacy Department, Faculty of Pharmacy, Ain Shams University, 11566 Cairo, Egypt
| | - Lillian Prince
- School of Public Health, University of Illinois at Chicago, Chicago, IL 60612, USA;
| | - Tia Jackson-Bey
- Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Illinois at Chicago, Chicago, IL 60612, USA;
| | - Ihor Atabiekov
- Moscow Region Cancer Center, Balashikha 143900, Russian;
| | - Stanisław Zgliczyński
- Department of Internal Diseases and Endocrinology, Central Teaching Clinical Hospital, Medical University of Warsaw, 02-097 Warsaw, Poland;
| | - Ayman Al-Hendy
- Department of Surgery, University of Illinois at Chicago, Chicago, IL 60612, USA;
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