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Li D, Jin P, Cai Y, Wu S, Guo X, Zhang Z, Liu K, Li P, Hu Y, Zhou Y. Clinical significance of lipid pathway-targeted therapy in breast cancer. Front Pharmacol 2025; 15:1514811. [PMID: 39834807 PMCID: PMC11743736 DOI: 10.3389/fphar.2024.1514811] [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: 10/21/2024] [Accepted: 12/17/2024] [Indexed: 01/22/2025] Open
Abstract
Globally, breast cancer represents the most common cancer and the primary cause of death by cancer in women. Lipids are crucial in human physiology, serving as vital energy reserves, structural elements of biological membranes, and essential signaling molecules. The metabolic reprogramming of lipid pathways has emerged as a critical factor in breast cancer progression, drug resistance, and patient prognosis. In this study, we delve into the clinical implications of lipid pathway-targeted therapy in breast cancer. We highlight key enzymes and potential therapeutic targets involved in lipid metabolism reprogramming, and their associations with cancer progression and treatment outcomes. Furthermore, we detail the clinical trials exploring the anticancer and cancer chemopreventive activity of therapies targeting these molecules. However, the clinical efficacy of these therapies remains controversial, highlighting the urgent need for predictive biomarkers to identify patient subpopulations likely to benefit from such treatment. We propose the Selective Lipid Metabolism Therapy Benefit Hypothesis, emphasizing the importance of personalized medicine in optimizing lipid pathway-targeted therapy for breast cancer patients.
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Affiliation(s)
- Dan Li
- Department of Breast Surgery and Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Pengcheng Jin
- Department of Surgical Oncology, Linhai Branch, The Second Affiliated Hospital, Zhejiang University School of Medicine, Taizhou, Zhejiang, China
| | - Yiqi Cai
- Department of Breast Surgery and Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Shijie Wu
- Department of Breast Surgery and Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xianan Guo
- Department of Breast Surgery and Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zhiyun Zhang
- Department of Breast Surgery and Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Kexin Liu
- Department of Breast Surgery and Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Panni Li
- Department of Breast Surgery and Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yue Hu
- Department of Breast Surgery and Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Yunxiang Zhou
- Department of Breast Surgery and Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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Pellegrino M, Occhiuzzi MA, Grande F, Pagani IS, Aquaro S, Tucci P. Modulation of energetic and lipid pathways by curcumin as a potential chemopreventive strategy in human prostate cancer cells. Biochem Biophys Res Commun 2024; 735:150477. [PMID: 39096884 DOI: 10.1016/j.bbrc.2024.150477] [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: 05/29/2024] [Revised: 07/19/2024] [Accepted: 07/29/2024] [Indexed: 08/05/2024]
Abstract
In Western industrialized countries, prostate cancer (PCa) is the second most common malignant disease and prevalent cause of death for men. Epidemiological studies have shown that curcumin (CUR) either prevents PCa initiation or delays its progression to a more aggressive and treatment-refractory form, thus reducing related mortality. Our previous studies have proven the anticancer, antioxidant, and anti-inflammatory properties of CUR on PCa cells. However, there are few reports of the effect of CUR on energy and lipid pathways in PCa. Herein, we show that CUR can modulate the two metabolic energy pathways, increasing glycolytic reserve and reducing oxidative phosphorylation. Moreover, through the regulation of key enzymes and proteins, CUR affected the lipid pathway in PC-3 to a greater extent compared to the healthy PNT-2 cells. According to molecular docking investigations, the CUR activity in PCa may be mediated by the direct binding to the pyruvate dehydrogenase (PDHA1) enzyme, which is essential for regulating the appropriate mitochondrial activity. Taken together, our results shed light on the mechanism of action of CUR in the PCa cell metabolism and provide evidence of its potential value as an anticancer metabolic modulator, paving opportunities for novel therapeutic strategies.
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Affiliation(s)
- Michele Pellegrino
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Rende, Italy.
| | | | - Fedora Grande
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Rende, Italy.
| | - Ilaria Stefania Pagani
- Cancer Program, Precision Medicine Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA 5000, Australia.
| | - Stefano Aquaro
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Rende, Italy.
| | - Paola Tucci
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Rende, Italy.
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Bhargav E, Mohammed N, Singh UN, Ramalingam P, Challa RR, Vallamkonda B, Ahmad SF, Dsnbk P, Pasala PK, Rudrapal M. A central composite design-based targeted quercetin nanoliposomal formulation: Optimization and cytotoxic studies on MCF-7 breast cancer cell lines. Heliyon 2024; 10:e37430. [PMID: 39296160 PMCID: PMC11409131 DOI: 10.1016/j.heliyon.2024.e37430] [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: 05/21/2024] [Revised: 09/02/2024] [Accepted: 09/03/2024] [Indexed: 09/21/2024] Open
Abstract
This study aimed to enhance the efficacy of quercetin (QT) by formulating it into a liposomal drug delivery system utilizing the concept of central composite design. The drug:lipid ratio, cholesterol concentration, and sonication time were selected as independent variables in the study. The vesicle and percentage entrapment efficiency were selected as the dependent variables. Quercetin nanoliposomes (QT-NLs) were prepared via a combination of ethanol injection and thin film hydration. The vesicle size and entrapment efficiency of all formulations were within the ranges of 100 nm and >80 %, respectively. The zeta potential value indicated the stability of the optimized formulation. The contour plots were used to select the desired batch range. SEM studies revealed an imperfect crystalline morphology without any unwanted agglomeration. MTT assays on VERO cell lines indicated the safety of the developed formulation. MTT assays of MCF-7 cells revealed IC50 values of 5.8 μM and 7.9 μM for QT-NLs and QT, respectively. In our study, the optimized formulation exhibited late and early apoptosis and necrosis when used to treat MCF-7 cells. S and G2/M cell cycle phases of MCF-7 cell arrest were confirmed by the cell cycle report. At sub-G0/G1 phase, 2.10 ± 1.1 %; G0/G1 phase, 34.13 ± 1.9 %; S phase, 34.55 ± 0.98 %; and G2/M phase, 26.24 ± 1.7 % of cell arrest were observed. The results demonstrated the effectiveness of the proposed design for the development of corn starch-coated QT-NLs and their activity in breast cancer cell lines.
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Affiliation(s)
- E Bhargav
- Raghavendra Institute of Pharmaceutical Education and Research, Anantapur, Andhra Pradesh, India
| | - Nawaz Mohammed
- Raghavendra Institute of Pharmaceutical Education and Research, Anantapur, Andhra Pradesh, India
| | - Udit Narayan Singh
- Raghavendra Institute of Pharmaceutical Education and Research, Anantapur, Andhra Pradesh, India
| | - P Ramalingam
- Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Hajipur, Bihar, India
| | - Ranadheer Reddy Challa
- Formulation and Development, Quotient Sciences, 3080 McCann Farm Dr, Garnet Valley, PA, USA
| | | | - Sheikh F Ahmad
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh-11451, Saudi Arabia
| | - Prasanth Dsnbk
- School of Pharmacy & Technology Management, SVKM's Narsee Monjee Institute of Management Studies (NMIMS), Jadcherla, Hyderabad, India
| | - Praveen Kumar Pasala
- Raghavendra Institute of Pharmaceutical Education and Research, Anantapur, Andhra Pradesh, India
| | - Mithun Rudrapal
- Department of Pharmaceutical Sciences, School of Biotechnology and Pharmaceutical Sciences, Vignan's Foundation for Science, Technology & Research, Guntur, Andhra Pradesh, India
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Shojaedini M, Hemadi M, Saki G, Fakhredini F, Khodayar MJ, Khorsandi L. Thymoquinone effects on autophagy, apoptosis, and oxidative stress in cisplatin-induced testicular damage in mice. J Assist Reprod Genet 2024; 41:1881-1891. [PMID: 38568464 PMCID: PMC11263301 DOI: 10.1007/s10815-024-03097-7] [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: 11/07/2023] [Accepted: 03/12/2024] [Indexed: 07/23/2024] Open
Abstract
PURPOSE In this study, the effect of thymoquinone (TQ) on CP-induced spermatogenesis defects in mice has been investigated. METHODS Sperm parameters, serum testosterone concentration, histology, Bax/Bcl-2 ratio, and expression of autophagy-related biomarkers have been assessed. Total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI) in testicular tissue were examined for the evaluation of oxidative stress levels. RESULTS CP has induced histological changes and significantly increased the Bax/Bcl-2 ratio, decreased testosterone concentration, testicular weight, and sperm quality. CP induced oxidative stress by elevating OSI in the testicular tissue (p < 0.05). Expression of the autophagy-inducer genes (ATG7, ATG5, and Beclin-1) and ratio of LC3B/LC3A proteins were significantly decreased, while mTOR expression was increased in the CP group. TQ pretreatment dose-dependently decreased the Bax/Bcl-2 ratio and mTOR gene expression while increasing the expression of ATG5 and ATG7 genes, LC3B/LC3A ratio, and Beclin-1 proteins. TQ could also dose-dependently reverse the histology, testosterone level, and sperm quality of the CP-intoxicated mice. CONCLUSIONS These findings show that TQ pretreatment can enhance sperm production by inducing autophagy and reducing apoptosis and oxidative stress in the CP-intoxicated mouse testicles.
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Affiliation(s)
- Mina Shojaedini
- Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Department of Anatomical Sciences, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Masoud Hemadi
- Department of Anatomical Sciences, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Fertility, Infertility and Perinatology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Ghasem Saki
- Department of Anatomical Sciences, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Fereshtehsadat Fakhredini
- Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Department of Anatomical Sciences, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mohammad Javad Khodayar
- Toxicology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Layasadat Khorsandi
- Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
- Department of Anatomical Sciences, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
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Mamun MAA, Rakib A, Mandal M, Kumar S, Singla B, Singh UP. Polyphenols: Role in Modulating Immune Function and Obesity. Biomolecules 2024; 14:221. [PMID: 38397458 PMCID: PMC10887194 DOI: 10.3390/biom14020221] [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: 12/30/2023] [Revised: 02/02/2024] [Accepted: 02/12/2024] [Indexed: 02/25/2024] Open
Abstract
Polyphenols, long-used components of medicinal plants, have drawn great interest in recent years as potential therapeutic agents because of their safety, efficacy, and wide range of biological effects. Approximately 75% of the world's population still use plant-based medicinal compounds, indicating the ongoing significance of phytochemicals for human health. This study emphasizes the growing body of research investigating the anti-adipogenic and anti-obesity functions of polyphenols. The functions of polyphenols, including phenylpropanoids, flavonoids, terpenoids, alkaloids, glycosides, and phenolic acids, are distinct due to changes in chemical diversity and structural characteristics. This review methodically investigates the mechanisms by which naturally occurring polyphenols mediate obesity and metabolic function in immunomodulation. To this end, hormonal control of hunger has the potential to inhibit pro-obesity enzymes such as pancreatic lipase, the promotion of energy expenditure, and the modulation of adipocytokine production. Specifically, polyphenols affect insulin, a hormone that is essential for regulating blood sugar, and they also play a role, in part, in a complex web of factors that affect the progression of obesity. This review also explores the immunomodulatory properties of polyphenols, providing insight into their ability to improve immune function and the effects of polyphenols on gut health, improving the number of commensal bacteria, cytokine production suppression, and immune cell mediation, including natural killer cells and macrophages. Taken together, continuous studies are required to understand the prudent and precise mechanisms underlying polyphenols' therapeutic potential in obesity and immunomodulation. In the interim, this review emphasizes a holistic approach to health and promotes the consumption of a wide range of foods and drinks high in polyphenols. This review lays the groundwork for future developments, indicating that the components of polyphenols and their derivatives may provide the answer to urgent worldwide health issues. This compilation of the body of knowledge paves the way for future discoveries in the global treatment of pressing health concerns in obesity and metabolic diseases.
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Affiliation(s)
| | | | | | | | | | - Udai P. Singh
- Department of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science Center, 881 Madison Avenue, Memphis, TN 38163, USA; (M.A.A.M.); (A.R.); (M.M.); (S.K.); (B.S.)
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6
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Li D, Cao D, Sun Y, Cui Y, Zhang Y, Jiang J, Cao X. The roles of epigallocatechin gallate in the tumor microenvironment, metabolic reprogramming, and immunotherapy. Front Immunol 2024; 15:1331641. [PMID: 38348027 PMCID: PMC10859531 DOI: 10.3389/fimmu.2024.1331641] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 01/15/2024] [Indexed: 02/15/2024] Open
Abstract
Cancer, a disease that modern medicine has not fully understood and conquered, with its high incidence and mortality, deprives countless patients of health and even life. According to global cancer statistics, there were an estimated 19.3 million new cancer cases and nearly 10 million cancer deaths in 2020, with the age-standardized incidence and mortality rates of 201.0 and 100.7 per 100,000, respectively. Although remarkable advancements have been made in therapeutic strategies recently, the overall prognosis of cancer patients remains not optimistic. Consequently, there are still many severe challenges to be faced and difficult problems to be solved in cancer therapy today. Epigallocatechin gallate (EGCG), a natural polyphenol extracted from tea leaves, has received much attention for its antitumor effects. Accumulating investigations have confirmed that EGCG can inhibit tumorigenesis and progression by triggering apoptosis, suppressing proliferation, invasion, and migration, altering tumor epigenetic modification, and overcoming chemotherapy resistance. Nevertheless, its regulatory roles and biomolecular mechanisms in the immune microenvironment, metabolic microenvironment, and immunotherapy remain obscure. In this article, we summarized the most recent updates about the effects of EGCG on tumor microenvironment (TME), metabolic reprogramming, and anti-cancer immunotherapy. The results demonstrated EGCG can promote the anti-cancer immune response of cytotoxic lymphocytes and dendritic cells (DCs), attenuate the immunosuppression of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), and inhibit the tumor-promoting functions of tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), and various stromal cells including cancer-associated fibroblasts (CAFs), endothelial cells (ECs), stellate cells, and mesenchymal stem/stromal cells (MSCs). Additionally, EGCG can suppress multiple metabolic reprogramming pathways, including glucose uptake, aerobic glycolysis, glutamine metabolism, fatty acid anabolism, and nucleotide synthesis. Finally, EGCG, as an immunomodulator and immune checkpoint blockade, can enhance immunotherapeutic efficacy and may be a promising candidate for antitumor immunotherapy. In conclusion, EGCG plays versatile regulatory roles in TME and metabolic reprogramming, which provides novel insights and combined therapeutic strategies for cancer immunotherapy.
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Affiliation(s)
- Dongming Li
- Department of Gastric and Colorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China
| | - Donghui Cao
- Division of Clinical Epidemiology, The First Hospital of Jilin University, Changchun, China
| | - Yuanlin Sun
- Department of Gastric and Colorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China
| | - Yingnan Cui
- Department of Gastric and Colorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China
| | - Yangyu Zhang
- Division of Clinical Epidemiology, The First Hospital of Jilin University, Changchun, China
| | - Jing Jiang
- Division of Clinical Epidemiology, The First Hospital of Jilin University, Changchun, China
| | - Xueyuan Cao
- Department of Gastric and Colorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China
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Kim DH, Song NY, Yim H. Targeting dysregulated lipid metabolism in the tumor microenvironment. Arch Pharm Res 2023; 46:855-881. [PMID: 38060103 PMCID: PMC10725365 DOI: 10.1007/s12272-023-01473-y] [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: 09/27/2023] [Accepted: 11/25/2023] [Indexed: 12/08/2023]
Abstract
The reprogramming of lipid metabolism and its association with oncogenic signaling pathways within the tumor microenvironment (TME) have emerged as significant hallmarks of cancer. Lipid metabolism is defined as a complex set of molecular processes including lipid uptake, synthesis, transport, and degradation. The dysregulation of lipid metabolism is affected by enzymes and signaling molecules directly or indirectly involved in the lipid metabolic process. Regulation of lipid metabolizing enzymes has been shown to modulate cancer development and to avoid resistance to anticancer drugs in tumors and the TME. Because of this, understanding the metabolic reprogramming associated with oncogenic progression is important to develop strategies for cancer treatment. Recent advances provide insight into fundamental mechanisms and the connections between altered lipid metabolism and tumorigenesis. In this review, we explore alterations to lipid metabolism and the pivotal factors driving lipid metabolic reprogramming, which exacerbate cancer progression. We also shed light on the latest insights and current therapeutic approaches based on small molecular inhibitors and phytochemicals targeting lipid metabolism for cancer treatment. Further investigations are worthwhile to fully understand the underlying mechanisms and the correlation between altered lipid metabolism and carcinogenesis.
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Affiliation(s)
- Do-Hee Kim
- Department of Chemistry, College of Convergence and Integrated Science, Kyonggi University, Suwon, 16227, Korea
| | - Na-Young Song
- Department of Applied Life Science, The Graduate School, BK21 Four Project, Yonsei University, Seoul, 03722, Korea
- Department of Oral Biology, Yonsei University College of Dentistry, Seoul, 03722, Korea
| | - Hyungshin Yim
- Department of Pharmacy, College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, 15588, Korea.
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Mallick R, Bhowmik P, Duttaroy AK. Targeting fatty acid uptake and metabolism in cancer cells: A promising strategy for cancer treatment. Biomed Pharmacother 2023; 167:115591. [PMID: 37774669 DOI: 10.1016/j.biopha.2023.115591] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 09/21/2023] [Accepted: 09/25/2023] [Indexed: 10/01/2023] Open
Abstract
Despite scientific development, cancer is still a fatal disease. The development of cancer is thought to be significantly influenced by fatty acids. Several mechanisms that control fatty acid absorption and metabolism are reported to be altered in cancer cells to support their survival. Cancer cells can use de novo synthesis or uptake of extracellular fatty acid if one method is restricted. This factor makes it more difficult to target one pathway while failing to treat the disease properly. Side effects may also arise if several inhibitors simultaneously target many targets. If a viable inhibitor could work on several routes, the number of negative effects might be reduced. Comparative investigations against cell viability have found several potent natural and manmade substances. In this review, we discuss the complex roles that fatty acids play in the development of tumors and the progression of cancer, newly discovered and potentially effective natural and synthetic compounds that block the uptake and metabolism of fatty acids, the adverse side effects that can occur when multiple inhibitors are used to treat cancer, and emerging therapeutic approaches.
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Affiliation(s)
- Rahul Mallick
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
| | - Prasenjit Bhowmik
- Department of Chemistry, Uppsala Biomedical Centre, Uppsala University, Sweden
| | - Asim K Duttaroy
- Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Norway.
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Hazimeh D, Massoud G, Parish M, Singh B, Segars J, Islam MS. Green Tea and Benign Gynecologic Disorders: A New Trick for An Old Beverage? Nutrients 2023; 15:1439. [PMID: 36986169 PMCID: PMC10054707 DOI: 10.3390/nu15061439] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Revised: 03/08/2023] [Accepted: 03/14/2023] [Indexed: 03/19/2023] Open
Abstract
Green tea is harvested from the tea plant Camellia sinensis and is one of the most widely consumed beverages worldwide. It is richer in antioxidants than other forms of tea and has a uniquely high content of polyphenolic compounds known as catechins. Epigallocatechin-3-gallate (EGCG), the major green tea catechin, has been studied for its potential therapeutic role in many disease contexts, including pathologies of the female reproductive system. As both a prooxidant and antioxidant, EGCG can modulate many cellular pathways important to disease pathogenesis and thus has clinical benefits. This review provides a synopsis of the current knowledge on the beneficial effects of green tea in benign gynecological disorders. Green tea alleviates symptom severity in uterine fibroids and improves endometriosis through anti-fibrotic, anti-angiogenic, and pro-apoptotic mechanisms. Additionally, it can reduce uterine contractility and improve the generalized hyperalgesia associated with dysmenorrhea and adenomyosis. Although its role in infertility is controversial, EGCG can be used as a symptomatic treatment for menopause, where it decreases weight gain and osteoporosis, as well as for polycystic ovary syndrome (PCOS).
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Affiliation(s)
| | | | | | | | - James Segars
- Department of Gynecology and Obstetrics, Division of Reproductive Sciences & Women’s Health Research, Johns Hopkins Medicine, Baltimore, MD 21205, USA
| | - Md Soriful Islam
- Department of Gynecology and Obstetrics, Division of Reproductive Sciences & Women’s Health Research, Johns Hopkins Medicine, Baltimore, MD 21205, USA
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10
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Sun W, Shahrajabian MH. Therapeutic Potential of Phenolic Compounds in Medicinal Plants-Natural Health Products for Human Health. Molecules 2023; 28:1845. [PMID: 36838831 PMCID: PMC9960276 DOI: 10.3390/molecules28041845] [Citation(s) in RCA: 176] [Impact Index Per Article: 88.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 02/11/2023] [Accepted: 02/13/2023] [Indexed: 02/18/2023] Open
Abstract
Phenolic compounds and flavonoids are potential substitutes for bioactive agents in pharmaceutical and medicinal sections to promote human health and prevent and cure different diseases. The most common flavonoids found in nature are anthocyanins, flavones, flavanones, flavonols, flavanonols, isoflavones, and other sub-classes. The impacts of plant flavonoids and other phenolics on human health promoting and diseases curing and preventing are antioxidant effects, antibacterial impacts, cardioprotective effects, anticancer impacts, immune system promoting, anti-inflammatory effects, and skin protective effects from UV radiation. This work aims to provide an overview of phenolic compounds and flavonoids as potential and important sources of pharmaceutical and medical application according to recently published studies, as well as some interesting directions for future research. The keyword searches for flavonoids, phenolics, isoflavones, tannins, coumarins, lignans, quinones, xanthones, curcuminoids, stilbenes, cucurmin, phenylethanoids, and secoiridoids medicinal plant were performed by using Web of Science, Scopus, Google scholar, and PubMed. Phenolic acids contain a carboxylic acid group in addition to the basic phenolic structure and are mainly divided into hydroxybenzoic and hydroxycinnamic acids. Hydroxybenzoic acids are based on a C6-C1 skeleton and are often found bound to small organic acids, glycosyl moieties, or cell structural components. Common hydroxybenzoic acids include gallic, syringic, protocatechuic, p-hydroxybenzoic, vanillic, gentistic, and salicylic acids. Hydroxycinnamic acids are based on a C6-C3 skeleton and are also often bound to other molecules such as quinic acid and glucose. The main hydroxycinnamic acids are caffeic, p-coumaric, ferulic, and sinapic acids.
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Affiliation(s)
- Wenli Sun
- Correspondence: ; Tel.: +86-13-4260-83836
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Insights on Dietary Polyphenols as Agents against Metabolic Disorders: Obesity as a Target Disease. Antioxidants (Basel) 2023; 12:antiox12020416. [PMID: 36829976 PMCID: PMC9952395 DOI: 10.3390/antiox12020416] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Revised: 02/02/2023] [Accepted: 02/02/2023] [Indexed: 02/11/2023] Open
Abstract
Obesity is a condition that leads to increased health problems associated with metabolic disorders. Synthetic drugs are available for obesity treatment, but some of these compounds have demonstrated considerable side effects that limit their use. Polyphenols are vital phytonutrients of plant origin that can be incorporated as functional food ingredients. This review presents recent developments in dietary polyphenols as anti-obesity agents. Evidence supporting the potential application of food-derived polyphenols as agents against obesity has been summarized. Literature evidence supports the effectiveness of plant polyphenols against obesity. The anti-obesity mechanisms of polyphenols have been explained by their potential to inhibit obesity-related digestive enzymes, modulate neurohormones/peptides involved in food intake, and their ability to improve the growth of beneficial gut microbes while inhibiting the proliferation of pathogenic ones. Metabolism of polyphenols by gut microbes produces different metabolites with enhanced biological properties. Thus, research demonstrates that dietary polyphenols can offer a novel path to developing functional foods for treating obesity. Upcoming investigations need to explore novel techniques, such as nanocarriers, to improve the content of polyphenols in foods and their delivery and bioavailability at the target sites in the body.
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Parish M, Massoud G, Hazimeh D, Segars J, Islam MS. Green Tea in Reproductive Cancers: Could Treatment Be as Simple? Cancers (Basel) 2023; 15:cancers15030862. [PMID: 36765820 PMCID: PMC9913717 DOI: 10.3390/cancers15030862] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 01/24/2023] [Accepted: 01/28/2023] [Indexed: 01/31/2023] Open
Abstract
Green tea originates from the tea plant Camellia sinensis and is one of the most widely consumed beverages worldwide. Green tea polyphenols, commonly known as catechins, are the major bioactive ingredients and account for green tea's unique health benefits. Epigallocatechin-3-gallate (EGCG), is the most potent catechin derivative and has been widely studied for its pro- and anti-oxidative effects. This review summarizes the chemical and chemopreventive properties of green tea in the context of female reproductive cancers. A comprehensive search of PubMed and Google Scholar up to December 2022 was conducted. All original and review articles related to green tea or EGCG, and gynecological cancers published in English were included. The findings of several in vitro, in vivo, and epidemiological studies examining the effect of green tea on reproductive cancers, including ovarian, cervical, endometrial, and vulvar cancers, are presented. Studies have shown that this compound targets specific receptors and intracellular signaling pathways involved in cancer pathogenesis. The potential benefits of using green tea in the treatment of reproductive cancers, alone or in conjunction with chemotherapeutic agents, are examined, shedding light on new therapeutic strategies for the management of female reproductive cancers.
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Affiliation(s)
| | | | | | - James Segars
- Correspondence: (J.S.); or (M.S.I.); Tel.: +1-410-614-2000 (J.S. & M.S.I.)
| | - Md Soriful Islam
- Correspondence: (J.S.); or (M.S.I.); Tel.: +1-410-614-2000 (J.S. & M.S.I.)
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13
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Phytochemical Compounds and Anticancer Activity of Cladanthus mixtus Extracts from Northern Morocco. Cancers (Basel) 2022; 15:cancers15010152. [PMID: 36612148 PMCID: PMC9818270 DOI: 10.3390/cancers15010152] [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: 11/22/2022] [Revised: 12/20/2022] [Accepted: 12/23/2022] [Indexed: 12/29/2022] Open
Abstract
Many of the chemotherapeutic drugs for the treatment of cancer are molecules identified and isolated from plants or their synthetic derivatives. This work aimed to identify the bioactive compounds using LC-MS and GC-MS and to evaluate the anticancer activity of the methanolic extracts of roots, stems, leaves, and flowers from Cladanthus mixtus. The anticancer activity was evaluated in vitro against two cancer cell lines: human breast carcinoma (MCF-7) and human prostate carcinoma (PC-3), using the MTT assay and microscopic observation. A human normal lung fibroblast (MRC-5) was included to determine the extract's safety for non-tumoral cells. The chemical composition results by LC-MS analysis revealed the presence of 24 phenolic compounds. Furthermore, GC-MS analysis allowed the identification of many biomolecules belonging to terpenoids, esters, alcohols, alkanes, fatty acids, organic acids, benzenes, phenols, ketones, carbonyls, amines, sterols, and other groups. The findings suggest that the majority of C. mixtus extracts have antiproliferative activity against two cancer cell lines, MCF-7 and PC-3, and one non-tumoral cell line, MRC-5. The activity was dose-dependent, and the highest effect was obtained with leaf extract in the two cancer cell lines. Moreover, these extracts demonstrated an acceptable toxicological profile against normal cells. Overall, C. mixtus extracts revealed promising antitumor properties provided by their phytochemical composition.
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14
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Li XX, Liu C, Dong SL, Ou CS, Lu JL, Ye JH, Liang YR, Zheng XQ. Anticarcinogenic potentials of tea catechins. Front Nutr 2022; 9:1060783. [PMID: 36545470 PMCID: PMC9760998 DOI: 10.3389/fnut.2022.1060783] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Accepted: 11/21/2022] [Indexed: 12/07/2022] Open
Abstract
Catechins are a cluster of polyphenolic bioactive components in green tea. Anticarcinogenic effects of tea catechins have been reported since the 1980s, but it has been controversial. The present paper reviews the advances in studies on the anticarcinogenic activities of tea and catechins, including epidemiological evidence and anticarcinogenic mechanism. Tea catechins showed antagonistic effects on many cancers, such as gynecological cancers, digestive tract cancers, incident glioma, liver and gallbladder cancers, lung cancer, etc. The mechanism underlying the anticarcinogenic effects of catechins involves in inhibiting the proliferation and growth of cancer cells, scavenging free radicals, suppressing metastasis of cancer cells, improving immunity, interacting with other anticancer drugs, and regulating signaling pathways. The inconsistent results and their causes are also discussed in this paper.
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Affiliation(s)
- Xiao-Xiang Li
- Tea Research Institute, Zhejiang University, Hangzhou, China
| | - Chang Liu
- Tea Science Society of China, Hangzhou, China
| | - Shu-Ling Dong
- Tea Research Institute, Zhejiang University, Hangzhou, China
| | - Can-Song Ou
- Development Center of Liubao Tea Industry, Cangwu, China
| | - Jian-Liang Lu
- Tea Research Institute, Zhejiang University, Hangzhou, China
| | - Jian-Hui Ye
- Tea Research Institute, Zhejiang University, Hangzhou, China
| | - Yue-Rong Liang
- Tea Research Institute, Zhejiang University, Hangzhou, China,*Correspondence: Yue-Rong Liang,
| | - Xin-Qiang Zheng
- Tea Research Institute, Zhejiang University, Hangzhou, China,Xin-Qiang Zheng,
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15
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Immunomodulatory, Anticancer, and Antimicrobial Effects of Rice Bran Grown in Iraq: An In Vitro and In Vivo Study. Pharmaceuticals (Basel) 2022; 15:ph15121502. [PMID: 36558953 PMCID: PMC9782048 DOI: 10.3390/ph15121502] [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: 11/05/2022] [Revised: 11/26/2022] [Accepted: 11/29/2022] [Indexed: 12/03/2022] Open
Abstract
Emerging evidence supports the role of rice bran in cancer prevention. Studies were conducted on multiple rice cultivars. However, limited studies were conducted on rice cultivars in the Middle East. In this study, rice bran growing in Iraq (O. sativa ssp. Japonica, cultivars: Amber Barka) was evaluated for its effect on preventing cancer and stimulating the immune system. Rice bran was collected from local mills in Al-Najaf (south of Iraq). Several solvent extracts (ethanol, methanol, n-hexane, and water) were prepared by maceration. MTT assay was used to measure the antiproliferative effects of extracts against a panel of cancer cell lines. The ability of each extract to induce apoptosis and inhibit angiogenesis was measured using standard ELISA kits. The effect of extracts on the immune system was evaluated using a lymphocyte proliferation assay, a pinocytic activity assay, a phagocytic activity assay, and a Th1/Th2 cytokine detection kit. A microbroth dilution method was used to detect the antimicrobial activity of each extract against different microbial strains. LC-MS analysis was used to detect the phytochemical composition of extracts, while DPPH assay was used to determine the antioxidant activity. For the in vivo study, rice bran was added to mouse fodder at 10% and 20%. Mice were treated for two weeks using mouse fodder supplemented with rice bran. In the third week of the experiment, EMT6/P breast cancer cells (1 × 10⁶ cells/mL) were injected subcutaneously into the abdominal area of each mouse. The dimensions of the grown tumors were measured after 14 days of tumor inoculation. A microbroth dilution method was used to evaluate the antimicrobial activity of rice bran extracts against three bacterial strains. The highest antiproliferative activity was observed in ethanol and n-hexane extracts. Ethanol and methanol extract showed the highest activity to induce apoptosis and inhibit angiogenesis. Both extracts were also effective to enhance immunity by activating lymphocytes and phagocytes proliferation with modulations of cytokine levels. The incorporation of rice bran in mice food caused a 20% regression in tumor development and growth compared with the negative control. All extracts exhibited limited antimicrobial activity against tested microorganisms. Methanol extract showed antioxidant activity with an IC50 value of 114 µg/mL. LC-MS analysis revealed the presence of multiple phytochemicals in rice bran including apiin, ferulic acid, and succinic acid. Rice bran is a rich source of active phytochemicals that may inhibit cancer and stimulate the immune system. Rice bran's biological activities could be due to the presence of multiple synergistically active phytochemicals. Further studies are needed to understand the exact mechanisms of action of rice bran.
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16
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Fan H, Guo Y, Zhang Y, Ding N, Liu M, Ma X, Yang J. α-Mangostin suppresses proliferation and invasion in osteosarcoma cells via inhibiting fatty acid synthase. J Funct Foods 2022. [DOI: 10.1016/j.jff.2022.105107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
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17
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α-Linolenic Acid Suppresses Proliferation and Invasion in Osteosarcoma Cells via Inhibiting Fatty Acid Synthase. Molecules 2022; 27:molecules27092741. [PMID: 35566090 PMCID: PMC9105512 DOI: 10.3390/molecules27092741] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 04/11/2022] [Accepted: 04/20/2022] [Indexed: 12/26/2022] Open
Abstract
Fatty acid synthase (FASN) is highly expressed in multiple types of human cancers and is recognized as one of the targets for treating cancer metastasis. α-Linolenic acid is an omega-3 essential fatty acid and it possesses various biological activities. The present study was designed to reveal the effects of α-linolenic acid on osteosarcoma and to reveal whether the mechanism of α-linolenic acid in anticancer activity may be related to FASN inhibition. The cytotoxicity of α-linolenic acid was assessed in osteosarcoma MG63, 143B, and U2OS cells. Cell viability was detected by the MTT assay. The protein expression level was detected by western blotting. Flow cytometry, Annexin V/propidium iodide dual staining, and Hoechst 33258 staining were performed to assess the apoptotic effects. Wound healing assay was applied to detect the inhibitory effect of α-linolenic acid on osteosarcoma cells migration. The results showed that α-linolenic acid downregulated FASN expression. α-Linolenic acid inhibited osteosarcoma cell proliferation and migration in a dose-dependent manner. In addition, α-linolenic acid regulated endoplasmic reticulum transmembrane receptors and signal protein expression in osteosarcoma cells. The findings of the present study suggested that α-linolenic acid suppresses osteosarcoma cell proliferation and metastasis by inhibiting FASN expression, which provides a basis as a potential target for osteosarcoma treatment.
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Kelly JM, Jeitner TM, Waterhouse NN, Qu W, Linstad EJ, Samani B, Williams C, Nikolopoulou A, Amor-Coarasa A, DiMagno SG, Babich JW. Synthesis and Evaluation of 11C-Labeled Triazolones as Probes for Imaging Fatty Acid Synthase Expression by Positron Emission Tomography. Molecules 2022; 27:1552. [PMID: 35268652 PMCID: PMC8911806 DOI: 10.3390/molecules27051552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Revised: 02/22/2022] [Accepted: 02/23/2022] [Indexed: 12/10/2022] Open
Abstract
Cancer cells require lipids to fulfill energetic, proliferative, and signaling requirements. Even though these cells can take up exogenous fatty acids, the majority exhibit a dependency on de novo fatty acid synthesis. Fatty acid synthase (FASN) is the rate-limiting enzyme in this process. Expression and activity of FASN is elevated in multiple cancers, where it correlates with disease progression and poor prognosis. These observations have sparked interest in developing methods of detecting FASN expression in vivo. One promising approach is the imaging of radiolabeled molecular probes targeting FASN by positron emission tomography (PET). However, although [11C]acetate uptake by prostate cancer cells correlates with FASN expression, no FASN-specific PET probes currently exist. Our aim was to synthesize and evaluate a series of small molecule triazolones based on GSK2194069, an FASN inhibitor with IC50 = 7.7 ± 4.1 nM, for PET imaging of FASN expression. These triazolones were labeled with carbon-11 in good yield and excellent radiochemical purity, and binding to FASN-positive LNCaP cells was significantly higher than FASN-negative PC3 cells. Despite these promising characteristics, however, these molecules exhibited poor in vivo pharmacokinetics and were predominantly retained in lymph nodes and the hepatobiliary system. Future studies will seek to identify structural modifications that improve tumor targeting while maintaining the excretion profile of these first-generation 11C-methyltriazolones.
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Affiliation(s)
- James M. Kelly
- Molecular Imaging Innovations Institute (MI3), Department of Radiology, Weill Cornell Medicine, New York, NY 10065, USA; (T.M.J.); (C.W.J.); (A.N.); (A.A.-C.); (J.W.B.)
- Citigroup Biomedical Imaging Center, Weill Cornell Medicine, New York, NY 10021, USA; (N.N.W.); (W.Q.)
| | - Thomas M. Jeitner
- Molecular Imaging Innovations Institute (MI3), Department of Radiology, Weill Cornell Medicine, New York, NY 10065, USA; (T.M.J.); (C.W.J.); (A.N.); (A.A.-C.); (J.W.B.)
| | - Nicole N. Waterhouse
- Citigroup Biomedical Imaging Center, Weill Cornell Medicine, New York, NY 10021, USA; (N.N.W.); (W.Q.)
| | - Wenchao Qu
- Citigroup Biomedical Imaging Center, Weill Cornell Medicine, New York, NY 10021, USA; (N.N.W.); (W.Q.)
| | - Ethan J. Linstad
- Departments of Medicinal Chemistry & Pharmacognosy and Chemistry, University of Illinois-Chicago, Chicago, IL 60612, USA; (E.J.L.); (B.S.); (S.G.D.)
- Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE 68588, USA
| | - Banafshe Samani
- Departments of Medicinal Chemistry & Pharmacognosy and Chemistry, University of Illinois-Chicago, Chicago, IL 60612, USA; (E.J.L.); (B.S.); (S.G.D.)
| | - Clarence Williams
- Molecular Imaging Innovations Institute (MI3), Department of Radiology, Weill Cornell Medicine, New York, NY 10065, USA; (T.M.J.); (C.W.J.); (A.N.); (A.A.-C.); (J.W.B.)
| | - Anastasia Nikolopoulou
- Molecular Imaging Innovations Institute (MI3), Department of Radiology, Weill Cornell Medicine, New York, NY 10065, USA; (T.M.J.); (C.W.J.); (A.N.); (A.A.-C.); (J.W.B.)
- Citigroup Biomedical Imaging Center, Weill Cornell Medicine, New York, NY 10021, USA; (N.N.W.); (W.Q.)
| | - Alejandro Amor-Coarasa
- Molecular Imaging Innovations Institute (MI3), Department of Radiology, Weill Cornell Medicine, New York, NY 10065, USA; (T.M.J.); (C.W.J.); (A.N.); (A.A.-C.); (J.W.B.)
| | - Stephen G. DiMagno
- Departments of Medicinal Chemistry & Pharmacognosy and Chemistry, University of Illinois-Chicago, Chicago, IL 60612, USA; (E.J.L.); (B.S.); (S.G.D.)
| | - John W. Babich
- Molecular Imaging Innovations Institute (MI3), Department of Radiology, Weill Cornell Medicine, New York, NY 10065, USA; (T.M.J.); (C.W.J.); (A.N.); (A.A.-C.); (J.W.B.)
- Citigroup Biomedical Imaging Center, Weill Cornell Medicine, New York, NY 10021, USA; (N.N.W.); (W.Q.)
- Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA
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19
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Vardhan S, Sahoo SK. Virtual screening by targeting proteolytic sites of furin and TMPRSS2 to propose potential compounds obstructing the entry of SARS-CoV-2 virus into human host cells. J Tradit Complement Med 2022; 12:6-15. [PMID: 33868970 PMCID: PMC8040387 DOI: 10.1016/j.jtcme.2021.04.001] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Revised: 03/31/2021] [Accepted: 04/06/2021] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND AND AIM The year 2020 begins with the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that cause the disease COVID-19, and continue till today. As of March 23, 2021, the outbreak has infected 124,313,054 worldwide with a total death of 2,735,707. The use of traditional medicines as an adjuvant therapy with western drugs can lower the fatality rate due to the COVID-19. Therefore, in silico molecular docking study was performed to search potential phytochemicals and drugs that can block the entry of SARS-CoV-2 into host cells by inhibiting the proteolytic cleavage activity of furin and TMPRSS2. EXPERIMENTAL PROCEDURE The protein-protein docking of the host proteases furin and TMPRSS2 was carried out with the virus spike (S) protein to examine the conformational details and residues involved in the complex formation. Subsequently, a library of 163 ligands containing phytochemicals and drugs was virtually screened to propose potential hits that can inhibit the proteolytic cleavage activity of furin and TMPRSS2. RESULTS AND CONCLUSION The phytochemicals like limonin, gedunin, eribulin, pedunculagin, limonin glycoside and betunilic acid bind at the active site of both furin and TMPRSS2. Limonin and gedunin found mainly in the citrus fruits and neem showed the highest binding energy at the active site of furin and TMPRSS2, respectively. The polyphenols found in green tea can also be useful in suppressing the furin activity. Among the drugs, the drug nafamostat may be more beneficial than the camostat in suppressing the activity of TMPRSS2.
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Affiliation(s)
- Seshu Vardhan
- Department of Chemistry, Sardar Vallabhbhai National Institute of Technology (SVNIT), Surat, 395007, Gujarat, India
| | - Suban K. Sahoo
- Department of Chemistry, Sardar Vallabhbhai National Institute of Technology (SVNIT), Surat, 395007, Gujarat, India
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20
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Chen X, Man GCW, Hung SW, Zhang T, Fung LWY, Cheung CW, Chung JPW, Li TC, Wang CC. Therapeutic effects of green tea on endometriosis. Crit Rev Food Sci Nutr 2021:1-14. [PMID: 34620005 DOI: 10.1080/10408398.2021.1986465] [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] [Indexed: 01/11/2023]
Abstract
Endometriosis is a chronic disorder characterized by the presence of endometrial glands and stroma outside the uterine cavity. It affects 8%-10% of women in their reproductive years, and represents a major clinical problem with deleterious social, sexual and reproductive consequences. Current treatment options include pain relief, hormonal intervention and surgical removal. However, these treatments are deemed unsatisfactory owing to varying success, significant side effects and high recurrence rates. Green tea and its major bioactive component, (-)-epigallocatechin gallate (EGCG), possess diverse biological properties, particularly anti-angiogenic, anti-proliferation, anti-metastasis, and apoptosis induction. In recent years, preclinical studies have proposed the use of green tea to inhibit the growth of endometriosis. Herein, the aim of this review is to summarize the potential therapeutic effects of green tea on molecular and cellular mechanism through inflammation, oxidative stress, invasion and adhesion, apoptosis and angiogenesis in endometriosis.
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Affiliation(s)
- Xiaoyan Chen
- Department of Obstetrics and Gynaecology, Shenzhen Baoan Women's and Children's Hospital, Shenzhen University, Shenzhen, China.,Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong
| | - Gene Chi Wai Man
- Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong.,Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong
| | - Sze Wan Hung
- Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong
| | - Tao Zhang
- Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong
| | - Linda Wen Ying Fung
- Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong
| | - Chun Wai Cheung
- Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong
| | - Jacqueline Pui Wah Chung
- Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong
| | - Tin Chiu Li
- Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong.,Li Ka Shing Institute of Health Sciences; School of Biomedical Sciences; Chinese University of Hong Kong-Sichuan University Joint Laboratory in Reproductive Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Chi Chiu Wang
- Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong.,Li Ka Shing Institute of Health Sciences; School of Biomedical Sciences; Chinese University of Hong Kong-Sichuan University Joint Laboratory in Reproductive Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong
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21
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Thomas P, Dong J. (-)-Epicatechin acts as a potent agonist of the membrane androgen receptor, ZIP9 (SLC39A9), to promote apoptosis of breast and prostate cancer cells. J Steroid Biochem Mol Biol 2021; 211:105906. [PMID: 33989703 DOI: 10.1016/j.jsbmb.2021.105906] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 04/19/2021] [Accepted: 04/27/2021] [Indexed: 01/07/2023]
Abstract
(-)-Epicatechin, a flavonoid present in high concentrations in foods such as green tea and cocoa, exerts beneficial and protective effects in numerous disease models, including anti-tumorigenesis and apoptosis in human breast and prostate cancer cells. Potential interactions of (-)-epicatechin and (+)-catechin with the membrane androgen receptor, ZIP9 (SLC39A9), which mediates androgen induction of apoptosis in these cancer cells, were investigated. Both (-)-epicatechin and (+)-catechin were effective competitors of [3H]-testosterone binding to PC-3 prostate cancer cells (nuclear androgen receptor-negative, nAR-null) overexpressing ZIP9 (PC3-ZIP9), with relative binding affinities of 75 % and 28 % that of testosterone, respectively. (-)-Epicatechin (200 nM) mimicked the effects of 100 nM testosterone in inducing apoptosis of PC3-ZIP9 cells, whereas (+)-catechin (concentration range 200 nM-1000 nM) did not significantly increase apoptosis and instead blocked the apoptotic response to testosterone. (-)-Epicatechin also activated androgen-dependent ZIP9 signaling pathways, inducing decreases in cAMP production and elevating intracellular free zinc levels, while (+)-catechin typically lacked these actions. Both (-)-epicatechin and (+)-catechin also bound to cell membranes of MDA-MB-468 breast cancer cells (nAR-null, high ZIP9 expression). MDA-MB-468 cells showed similar apoptotic, cAMP, and free zinc signaling responses to (-)-epicatechin to those observed in PC3-ZIP9 cells, as well as antagonism by (+)-catechin of testosterone-induced apoptosis and modulation of cAMP and caspase-3 levels. Moreover, knockdown of ZIP9 expression in MDA-MB-468 cells with siRNA decreased specific [3H]-testosterone binding of both catechins and blocked the apoptotic and free zinc responses to testosterone and (-)-epicatechin. The results indicate (-)-epicatechin is a potent ZIP9 agonist in breast and prostate cancer cells.
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Affiliation(s)
- Peter Thomas
- Marine Science Institute, University of Texas at Austin, 750 Channel View Drive, Port Aransas, TX, 78373, United States.
| | - Jing Dong
- Marine Science Institute, University of Texas at Austin, 750 Channel View Drive, Port Aransas, TX, 78373, United States
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22
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Paiva P, Medina FE, Viegas M, Ferreira P, Neves RPP, Sousa JPM, Ramos MJ, Fernandes PA. Animal Fatty Acid Synthase: A Chemical Nanofactory. Chem Rev 2021; 121:9502-9553. [PMID: 34156235 DOI: 10.1021/acs.chemrev.1c00147] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Fatty acids are crucial molecules for most living beings, very well spread and conserved across species. These molecules play a role in energy storage, cell membrane architecture, and cell signaling, the latter through their derivative metabolites. De novo synthesis of fatty acids is a complex chemical process that can be achieved either by a metabolic pathway built by a sequence of individual enzymes, such as in most bacteria, or by a single, large multi-enzyme, which incorporates all the chemical capabilities of the metabolic pathway, such as in animals and fungi, and in some bacteria. Here we focus on the multi-enzymes, specifically in the animal fatty acid synthase (FAS). We start by providing a historical overview of this vast field of research. We follow by describing the extraordinary architecture of animal FAS, a homodimeric multi-enzyme with seven different active sites per dimer, including a carrier protein that carries the intermediates from one active site to the next. We then delve into this multi-enzyme's detailed chemistry and critically discuss the current knowledge on the chemical mechanism of each of the steps necessary to synthesize a single fatty acid molecule with atomic detail. In line with this, we discuss the potential and achieved FAS applications in biotechnology, as biosynthetic machines, and compare them with their homologous polyketide synthases, which are also finding wide applications in the same field. Finally, we discuss some open questions on the architecture of FAS, such as their peculiar substrate-shuttling arm, and describe possible reasons for the emergence of large megasynthases during evolution, questions that have fascinated biochemists from long ago but are still far from answered and understood.
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Affiliation(s)
- Pedro Paiva
- LAQV, REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre s/n, 4169-007 Porto, Portugal
| | - Fabiola E Medina
- Departamento de Ciencias Químicas, Facultad de Ciencias Exactas, Universidad Andres Bello, Autopista Concepción-Talcahuano, 7100 Talcahuano, Chile
| | - Matilde Viegas
- LAQV, REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre s/n, 4169-007 Porto, Portugal
| | - Pedro Ferreira
- LAQV, REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre s/n, 4169-007 Porto, Portugal
| | - Rui P P Neves
- LAQV, REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre s/n, 4169-007 Porto, Portugal
| | - João P M Sousa
- LAQV, REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre s/n, 4169-007 Porto, Portugal
| | - Maria J Ramos
- LAQV, REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre s/n, 4169-007 Porto, Portugal
| | - Pedro A Fernandes
- LAQV, REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre s/n, 4169-007 Porto, Portugal
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23
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Ligorio F, Pellegrini I, Castagnoli L, Vingiani A, Lobefaro R, Zattarin E, Santamaria M, Pupa SM, Pruneri G, de Braud F, Vernieri C. Targeting lipid metabolism is an emerging strategy to enhance the efficacy of anti-HER2 therapies in HER2-positive breast cancer. Cancer Lett 2021; 511:77-87. [PMID: 33961924 DOI: 10.1016/j.canlet.2021.04.023] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Revised: 04/23/2021] [Accepted: 04/26/2021] [Indexed: 12/24/2022]
Abstract
De novo or acquired resistance of cancer cells to currently available Human Epidermal Growth Factor Receptor 2 (HER2) inhibitors represents a clinical challenge. Several resistance mechanisms have been identified in recent years, with lipid metabolism reprogramming, a well-established hallmark of cancer, representing the last frontier of preclinical and clinical research in this field. Fatty Acid Synthase (FASN), the key enzyme required for fatty acids (FAs) biosynthesis, is frequently overexpressed/activated in HER2-positive (HER2+) breast cancer (BC), and it crucially sustains HER2+ BC cell growth, proliferation and survival. After the synthesis of new, selective and well tolerated FASN inhibitors, clinical trials have been initiated to test if these compounds are able to re-sensitize cancer cells with acquired resistance to HER2 inhibition. More recently, the upregulation of FA uptake by cancer cells has emerged as a potentially new and targetable mechanism of resistance to anti-HER2 therapies in HER2+ BC, thus opening a new era in the field of targeting metabolic reprogramming in clinical setting. Here, we review the available preclinical and clinical evidence supporting the inhibition of FA biosynthesis and uptake in combination with anti-HER2 therapies in patients with HER2+ BC, and we discuss ongoing clinical trials that are investigating these combination approaches.
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Affiliation(s)
- Francesca Ligorio
- Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy
| | - Ilaria Pellegrini
- Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy
| | - Lorenzo Castagnoli
- Molecular Targeting Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133, Milan, Italy
| | - Andrea Vingiani
- Pathology Department, Fondazione IRCCS Istituto Nazionale Tumori, Via Venezian 1, 20133, Milan, Italy; Department of Oncology and Haematology, University of Milan, Via Festa del Perdono 7, 20122, Milan, Italy
| | - Riccardo Lobefaro
- Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy
| | - Emma Zattarin
- Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy
| | - Marzia Santamaria
- IFOM, the FIRC Institute of Molecular Oncology, Via Adamello 16, Milan, Italy
| | - Serenella M Pupa
- Molecular Targeting Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133, Milan, Italy
| | - Giancarlo Pruneri
- Pathology Department, Fondazione IRCCS Istituto Nazionale Tumori, Via Venezian 1, 20133, Milan, Italy; Department of Oncology and Haematology, University of Milan, Via Festa del Perdono 7, 20122, Milan, Italy
| | - Filippo de Braud
- Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy; Department of Oncology and Haematology, University of Milan, Via Festa del Perdono 7, 20122, Milan, Italy
| | - Claudio Vernieri
- Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy; IFOM, the FIRC Institute of Molecular Oncology, Via Adamello 16, Milan, Italy.
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Zhao H, Mei K, Yang L, Liu X, Xie L. Green tea consumption and risk for esophageal cancer: A systematic review and dose-response meta-analysis. Nutrition 2021; 87-88:111197. [PMID: 33744644 DOI: 10.1016/j.nut.2021.111197] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 01/25/2021] [Accepted: 02/03/2021] [Indexed: 10/22/2022]
Abstract
OBJECTIVE Controversial results of the association between green tea consumption and risk for esophageal cancer (EC) were reported by previous meta-analysis. Thus, the aim of this study was to quantitatively investigate the association. METHODS The Cochrane Library, PubMed, and EMBASE databases were searched for relevant studies. We used a "one-stage approach" with a restricted cubic spline model to summarize the dose-specific relationships between green tea and risk for EC. Odds ratios (ORs) were used to measure the effects. Fourteen studies were included with a total of 5057 ECs among 493 332 participants. RESULTS In the dose-response analysis, the summary OR for a 1 cup/d increase in green tea was 1.00 (95% confidence interval [CI], 0.95-1.04; I2 = 77%). No nonlinearity association was observed between tea consumption and risk for EC (P = 0.71 for nonlinearity). In the subgroup of sex, the summary OR for a 1 cup/d increase in green tea was 1.03 (95% CI, 0.95-1.11, I2 = 67%) for men and 0.79 (95% CI, 0.68-0.91; I2 = 0%) for women. CONCLUSION Contrary to previous studies, based on current evidence, the present dose-response study suggested no association between green tea and risk for EC. However, there might be a protective effect of green tea in women. Notably, our conclusion might be influenced by limited studies and potential bias, such as dose of green tea assessment and select bias of case-control studies. Further larger number, prospective, and well-designed larger-scale studies are needed to provide more precise evidence, especially in women and more regions (United States and Europe).
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Affiliation(s)
- Huilei Zhao
- Department of Anesthesiology, The Third Hospital of Nanchang, Nanchang, Jiangxi, China
| | - Kaibo Mei
- Department of Anesthesiology, Shangrao People's Hospital, Shangrao, Jiangxi, China
| | - Lun Yang
- Thoracic Surgery Department, The First Affiliated Hospital of Nanchang University, Jiangxi, China
| | - Xiao Liu
- Department of Cardiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, PR China; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, China.
| | - Lixia Xie
- Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanchang University, Jiangxi, China.
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Montenegro I, Moreira J, Ramírez I, Dorta F, Sánchez E, Alfaro JF, Valenzuela M, Jara-Gutiérrez C, Muñoz O, Alvear M, Werner E, Madrid A, Villena J, Seeger M. Chemical Composition, Antioxidant and Anticancer Activities of Leptocarpha rivularis DC Flower Extracts. Molecules 2020; 26:molecules26010067. [PMID: 33375633 PMCID: PMC7795695 DOI: 10.3390/molecules26010067] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2020] [Revised: 12/21/2020] [Accepted: 12/23/2020] [Indexed: 12/20/2022] Open
Abstract
An evaluation of antioxidant and anticancer activity was screened in Leptocarpha rivularis DC flower extracts using four solvents (n-hexane (Hex), dichloromethane (DCM), ethyl acetate (AcOEt), and ethanol (EtOH)). Extracts were compared for total extract flavonoids and phenol contents, antioxidant activity (2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH), ferric reducing antioxidant potential (FRAP), total reactive antioxidant properties (TRAP) and oxygen radical absorbance capacity (ORAC)) across a determined value of reduced/oxidized glutathione (GSH/GSSG), and cell viability (the sulforhodamine B (SRB) assay). The most active extracts were analyzed by chromatographic analysis (GC/MS) and tested for apoptotic pathways. Extracts from Hex, DCM and AcOEt reduced cell viability, caused changes in cell morphology, affected mitochondrial membrane permeability, and induced caspase activation in tumor cell lines HT-29, PC-3, and MCF-7. These effects were generally less pronounced in the HEK-293 cell line (nontumor cells), indicating clear selectivity towards tumor cell lines. We attribute likely extract activity to the presence of sesquiterpene lactones, in combination with other components like steroids and flavonoids.
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Affiliation(s)
- Iván Montenegro
- Escuela de Obstetricia y Puericultura, Facultad de Medicina, Universidad de Valparaíso, Angamos 655, Reñaca, Viña del Mar 2520000, Chile;
- Correspondence: (I.M.); (A.M.); (J.V.); (M.S.); Tel.: +56-322603046 (I.M.)
| | - Jorge Moreira
- Escuela de Obstetricia y Puericultura, Facultad de Medicina, Universidad de Valparaíso, Angamos 655, Reñaca, Viña del Mar 2520000, Chile;
| | - Ingrid Ramírez
- Centro de Biotecnología “Dr. Daniel Alkalay Lowitt”, Universidad Técnica Federico Santa María, Avda. España 1680, Valparaíso 2390123, Chile; (I.R.); (F.D.); (E.S.); (J.F.A.)
| | - Fernando Dorta
- Centro de Biotecnología “Dr. Daniel Alkalay Lowitt”, Universidad Técnica Federico Santa María, Avda. España 1680, Valparaíso 2390123, Chile; (I.R.); (F.D.); (E.S.); (J.F.A.)
| | - Elizabeth Sánchez
- Centro de Biotecnología “Dr. Daniel Alkalay Lowitt”, Universidad Técnica Federico Santa María, Avda. España 1680, Valparaíso 2390123, Chile; (I.R.); (F.D.); (E.S.); (J.F.A.)
| | - Juan Felipe Alfaro
- Centro de Biotecnología “Dr. Daniel Alkalay Lowitt”, Universidad Técnica Federico Santa María, Avda. España 1680, Valparaíso 2390123, Chile; (I.R.); (F.D.); (E.S.); (J.F.A.)
| | - Manuel Valenzuela
- Laboratorio de Microbiología Celular, Instituto de Investigación e Innovación en Salud, Facultad de Ciencias de la Salud, Universidad Central de Chile, Santiago 8320000, Chile;
| | - Carlos Jara-Gutiérrez
- Centro de Investigaciones Biomédicas (CIB), Laboratorio de Estrés Oxidativo, Escuela de Kinesiología, Facultad de Medicina, Universidad de Valparaíso, Viña del Mar 2520000, Chile;
| | - Ociel Muñoz
- Institute of Food Science and Technology, University Austral of Chile, Valdivia 5090000, Chile;
| | - Matias Alvear
- Laboratory of Industrial Chemistry, Process Chemistry Centre, Åbo Akademi University, Biskopsgatan 8, FIN-20500 Turku/Åbo, Finland;
| | - Enrique Werner
- Departamento de Ciencias Básicas, Campus Fernando May, Universidad del Bío-Bío, Avda. Andrés Bello 720, Casilla 447, Chillán 3780000, Chile;
| | - Alejandro Madrid
- Laboratorio de Productos Naturales y Síntesis Orgánica (LPNSO), Departamento de Química, Facultad de Ciencias Naturales y Exactas, Universidad de Playa Ancha, Avda. Leopoldo Carvallo 270, Playa Ancha, Valparaíso 2340000, Chile
- Correspondence: (I.M.); (A.M.); (J.V.); (M.S.); Tel.: +56-322603046 (I.M.)
| | - Joan Villena
- Centro de Investigaciones Biomédicas (CIB), Facultad de Medicina, Campus de la Salud, Universidad de Valparaíso, Angamos 655, Reñaca, Viña del Mar 2520000, Chile
- Correspondence: (I.M.); (A.M.); (J.V.); (M.S.); Tel.: +56-322603046 (I.M.)
| | - Michael Seeger
- Centro de Biotecnología “Dr. Daniel Alkalay Lowitt”, Universidad Técnica Federico Santa María, Avda. España 1680, Valparaíso 2390123, Chile; (I.R.); (F.D.); (E.S.); (J.F.A.)
- Laboratorio de Microbiología Molecular y Biotecnología Ambiental, Departamento de Química, Universidad Técnica Federico Santa María, Avda. España 1680, Valparaíso 2390123, Chile
- Correspondence: (I.M.); (A.M.); (J.V.); (M.S.); Tel.: +56-322603046 (I.M.)
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Altundag EM, Gençalp D, Özbilenler C, Toprak K, Kerküklü N. In vitro antioxidant, anti-inflammatory and anti-cancer activities of methanolic extract of Asparagus horridus grows in North Cyprus Kuzey Kıbrıs da yetişen Asparagus horridus metanolik ekstraktının in-vitro antioksidan, anti-enflamatuar ve anti-kanser aktivitesi. TURKISH JOURNAL OF BIOCHEMISTRY 2020. [DOI: 10.1515/tjb-2019-0325] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Abstract
Background
Asparagus horridus is an edible plant known as “Ayrelli” in North Cyprus. The scientific literature has not yet submitted a report about the antioxidant, anti-inflammatory and anti-cancer activities of A. horridus plant from North Cyprus until now. The purpose of the research was to determine the antioxidant, anti-inflammatory and anti-cancer activities of A. horridus.
Materials and methods
Soxhlet extraction of A. horridus was performed using methanol. Antioxidant activity was determined by DPPH, TFC, FRAP and TPC assays. Protein-denaturation assay was performed to determine the anti-inflammatory effect. The anti-cancer effects of the extract on HepG2 and B-CPAP cell lines were determined with MTT assay.
Results
Antioxidant activity for A. horridus extract was determined by DPPH (50%), TFC (266.26 μg QUE/mg extract), FRAP (1.27 μg FeSO4/mg extract) and TPC (167.613 μg GAE/mg extract) assays at 25 mg/mL. Inhibition of protein-denaturation activity was found as 29.42% at 25 mg/mL. After 24 h of the extract treatment, cell proliferation of HepG2 and B-CPAP cancer cells were inhibited at IC50 values 63.24 μg/mL and 101.24 μg/mL, respectively.
Conclusion
These results have shown that the methanol extract of A. horridus grows in North Cyprus has antioxidant, anti-inflammatory and anti-cancer activities.
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Affiliation(s)
- Ergul Mutlu Altundag
- Eastern Mediterranean University, Faculty of Medicine, Medical Biochemistry , North Cyprus via Mersin 10, Famagusta 99628, North Cyprus , Turkey
| | - Duygu Gençalp
- Eastern Mediterranean University, Faculty of Medicine, Medical Biochemistry , Famagusta, North Cyprus , Turkey
| | - Cahit Özbilenler
- Eastern Mediterranean University , Faculty of Art and Sciences, Chemistry , Famagusta, North Cyprus , Turkey
| | - Kübra Toprak
- Marmara Universitesi, Genetic and Metabolic Diseases Research Center , Istanbul , Turkey
| | - Namık Kerküklü
- Eastern Mediterranean University , Faculty of Art and Sciences, Chemistry , Famagusta, North Cyprus , Turkey
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Fontana F, Raimondi M, Marzagalli M, Di Domizio A, Limonta P. Natural Compounds in Prostate Cancer Prevention and Treatment: Mechanisms of Action and Molecular Targets. Cells 2020; 9:cells9020460. [PMID: 32085497 PMCID: PMC7072821 DOI: 10.3390/cells9020460] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2019] [Revised: 02/10/2020] [Accepted: 02/15/2020] [Indexed: 02/06/2023] Open
Abstract
Prostate cancer (PCa) represents a major cause of cancer mortality among men in developed countries. Patients with recurrent disease initially respond to androgen-deprivation therapy, but the tumor eventually progresses into castration-resistant PCa; in this condition, tumor cells acquire the ability to escape cell death and develop resistance to current therapies. Thus, new therapeutic approaches for PCa management are urgently needed. In this setting, natural products have been extensively studied for their anti-PCa activities, such as tumor growth suppression, cell death induction, and inhibition of metastasis and angiogenesis. Additionally, numerous studies have shown that phytochemicals can specifically target the androgen receptor (AR) signaling, as well as the PCa stem cells (PCSCs). Interestingly, many clinical trials have been conducted to test the efficacy of nutraceuticals in human subjects, and they have partially confirmed the promising results obtained in vitro and in preclinical models. This article summarizes the anti-cancer mechanisms and therapeutic potentials of different natural compounds in the context of PCa prevention and treatment.
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Affiliation(s)
- Fabrizio Fontana
- Department of Pharmacological and Biomolecular Sciences, University of Milano, 20133 Milano, Italy; (F.F.); (M.R.); (M.M.); (A.D.D.)
| | - Michela Raimondi
- Department of Pharmacological and Biomolecular Sciences, University of Milano, 20133 Milano, Italy; (F.F.); (M.R.); (M.M.); (A.D.D.)
| | - Monica Marzagalli
- Department of Pharmacological and Biomolecular Sciences, University of Milano, 20133 Milano, Italy; (F.F.); (M.R.); (M.M.); (A.D.D.)
| | - Alessandro Di Domizio
- Department of Pharmacological and Biomolecular Sciences, University of Milano, 20133 Milano, Italy; (F.F.); (M.R.); (M.M.); (A.D.D.)
- SPILLOproject, 20037 Paderno Dugnano, Italy
| | - Patrizia Limonta
- Department of Pharmacological and Biomolecular Sciences, University of Milano, 20133 Milano, Italy; (F.F.); (M.R.); (M.M.); (A.D.D.)
- Correspondence: ; Tel.: +39-0250318213
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Liberal J, Costa G, Carmo A, Vitorino R, Marques C, Domingues MR, Domingues P, Gonçalves AC, Alves R, Sarmento-Ribeiro AB, Girão H, Cruz MT, Batista MT. Chemical characterization and cytotoxic potential of an ellagitannin-enriched fraction from Fragaria vesca leaves. ARAB J CHEM 2019. [DOI: 10.1016/j.arabjc.2015.11.014] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
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Bisol Â, de Campos PS, Lamers ML. Flavonoids as anticancer therapies: A systematic review of clinical trials. Phytother Res 2019; 34:568-582. [PMID: 31752046 DOI: 10.1002/ptr.6551] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Revised: 09/25/2019] [Accepted: 10/28/2019] [Indexed: 12/17/2022]
Abstract
Flavonoids have been proposed as potential chemotherapeutic agents because they are toxic against cancer cells but not harmful to healthy cells. This systematic review analyzed flavonoid effectiveness in human cancer chemotherapy. Overall, 22 phase II and 1 phase III clinical trials (PubMed, Scopus, and Web of Science) that used flavonoids as a single agent or combined with other therapeutics against hematopoietic/lymphoid or solid cancer published by January 2019 were selected for analysis. Flavopiridol was the most commonly used flavonoid (at a dose of 50-mg/m2 IV) for all tumor types. Aside from the relatively low rate of complete response (CR) or partial response (PR) with any administration protocol, flavonoids showed higher positive outcomes for hematopoietic and lymphoid tissues (140 patients with CR and 88 with PR among 615 patients in 11 trials) than for solid tumors (4 patients with CR and 21 with PR among 525 patients in 12 trials). However, because of the high variety in administration schedule, more studies are needed to further understand how flavonoids can promote positive outcomes for cancer patients.
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Affiliation(s)
- Ângela Bisol
- Basic Research Center in Dentistry, Dentistry School, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
| | - Paloma Santos de Campos
- Basic Research Center in Dentistry, Dentistry School, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
| | - Marcelo Lazzaron Lamers
- Basic Research Center in Dentistry, Dentistry School, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.,Department of Morphological Sciences, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
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Sun LR, Zhou W, Zhang HM, Guo QS, Yang W, Li BJ, Sun ZH, Gao SH, Cui RJ. Modulation of Multiple Signaling Pathways of the Plant-Derived Natural Products in Cancer. Front Oncol 2019; 9:1153. [PMID: 31781485 PMCID: PMC6856297 DOI: 10.3389/fonc.2019.01153] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Accepted: 10/16/2019] [Indexed: 12/24/2022] Open
Abstract
Natural compounds are highly effective anticancer chemotherapeutic agents, and the targets of plant-derived anticancer agents have been widely reported. In this review, we focus on the main signaling pathways of apoptosis, proliferation, invasion, and metastasis that are regulated by polyphenols, alkaloids, saponins, and polysaccharides. Alkaloids primarily affect apoptosis-related pathways, while polysaccharides primarily target pathways related to proliferation, invasion, and metastasis. Other compounds, such as flavonoids and saponins, affect all of these aspects. The association between compound structures and signaling pathways may play a critical role in drug discovery.
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Affiliation(s)
- Li-Rui Sun
- Department of Pharmacy, The First Hospital of Jilin University, Changchun, China
| | - Wei Zhou
- Department of Pharmacy, The First Hospital of Jilin University, Changchun, China
| | - Hong-Mei Zhang
- Department of Pharmacy, The First Hospital of Jilin University, Changchun, China
| | - Qiu-Shi Guo
- Department of Pharmacy, The First Hospital of Jilin University, Changchun, China
| | - Wei Yang
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetic, The Second Hospital of Jilin University, Changchun, China
| | - Bing-Jin Li
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetic, The Second Hospital of Jilin University, Changchun, China
| | - Zhi-Hui Sun
- Department of Pharmacy, The First Hospital of Jilin University, Changchun, China
| | - Shuo-Hui Gao
- Department of Gastrointestinal Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Ran-Ji Cui
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetic, The Second Hospital of Jilin University, Changchun, China
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Tan YJ, Ali A, Tee SY, Teo JT, Xi Y, Go ML, Lam Y. Galloyl esters of trans-stilbenes are inhibitors of FASN with anticancer activity on non-small cell lung cancer cells. Eur J Med Chem 2019; 182:111597. [DOI: 10.1016/j.ejmech.2019.111597] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Revised: 07/17/2019] [Accepted: 08/05/2019] [Indexed: 12/16/2022]
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Wihadmadyatami H, Karnati S, Hening P, Tjahjono Y, Rizal, Maharjanti F, Kusindarta DL, Triyono T, Supriatno. Ethanolic extract Ocimum sanctum Linn. induces an apoptosis in human lung adenocarcinoma (A549) cells. Heliyon 2019; 5:e02772. [PMID: 31844708 PMCID: PMC6895684 DOI: 10.1016/j.heliyon.2019.e02772] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Revised: 08/13/2019] [Accepted: 10/29/2019] [Indexed: 12/29/2022] Open
Abstract
Ocimum sanctum (OS) is tropical herbal plant which is easy to find and widely used as a vegetable food in Indonesia. In last decade, lung adenocarcinoma was in top position as male cancer disease in Indonesia. Recently, emerging data showing the extracts of different species of Ocimum exhibiting the anti-tumor properties. Further studies on lung lewis carcinoma demonstrated pro-apoptosis effects after the treatment with Ocimum extracts. However, the effect of OS of Indonesian origin in human alveolar pulmonary adenocarcinoma A549 cells remain unclear. Therefore, we aimed to investigate effects of ethanolic extract OS (EEOS) in A549 cell culture systems. Cell adhesion and viability assays revealed that EEOS significantly decreased the attachment into extracellular matrix of A549 cells. Morphological examination AO/EB and DAPI staining indicated that EEOS induced the cells shrinkage, DNA fragmentation and condensation of A549 cells. Further, EEOS treatment induced the apoptosis rate followed by up-regulation of reactive oxygen species (ROS), caspase-3 expression and decreased anti-apoptotic protein Bcl-2. This condition also suppressed the expression of SOD2 as well as the GPx. In conclusion, our findings indicate that EEOS suppressed the viability of A549 cells, which may result from the activation of ROS promoting the apoptosis signaling via mitochondrial intrinsic pathway. Taken together, EEOS might be a good therapeutic potential to further understand its properties in the treatment of lung carcinoma.
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Affiliation(s)
- Hevi Wihadmadyatami
- Department of Anatomy, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia, 55281
| | - Srikanth Karnati
- Department of Anatomy and Cell Biology, Julius Maxilimilian University Wurzburg, Germany
| | - Puspa Hening
- Integrated Laboratory for Research and Testing, Universitas Gadjah Mada, Yogyakarta, Indonesia, 55281
| | - Yudy Tjahjono
- Faculty of Pharmacy, Widya Mandala Catholic University, Surabaya, Indonesia, 60265
| | - Rizal
- Biomolecular and Biomedical Research Center, Aretha Medika Utama, Bandung, Indonesia
| | - Fitriana Maharjanti
- Integrated Laboratory for Research and Testing, Universitas Gadjah Mada, Yogyakarta, Indonesia, 55281
| | - Dwi Liliek Kusindarta
- Department of Anatomy, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia, 55281
| | - Teguh Triyono
- Department of Clinical Pathology, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia, 55281
| | - Supriatno
- Department of Oral Medicine, Faculty of Dentistry, Universitas Gadjah Mada, Yogyakarta, Indonesia, 55281
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Carvalho TM, Cardoso HJ, Figueira MI, Vaz CV, Socorro S. The peculiarities of cancer cell metabolism: A route to metastasization and a target for therapy. Eur J Med Chem 2019; 171:343-363. [PMID: 30928707 DOI: 10.1016/j.ejmech.2019.03.053] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 03/19/2019] [Accepted: 03/21/2019] [Indexed: 02/06/2023]
Abstract
The last decade has witnessed the peculiarities of metabolic reprogramming in tumour onset and progression, and their relevance in cancer therapy. Also, it has been indicated that the metastatic process may depend on the metabolic rewiring and adaptation of cancer cells to the pressure of tumour microenvironment and limiting nutrient availability. The present review gatherers the existent knowledge on the influence of tumour microenvironment and metabolic routes driving metastasis. A focus will be given to glycolysis, fatty acid metabolism, glutaminolysis, and amino acid handling. In addition, the role of metabolic waste driving metastasization will be explored. Finally, we discuss the status of cancer treatment approaches targeting metabolism. This knowledge revision will highlight the critical metabolic targets in metastasis and the chemicals already used in preclinical studies and clinical trials, providing clues that would be further exploited in medicinal chemistry research.
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Affiliation(s)
- Tiago Ma Carvalho
- CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal
| | - Henrique J Cardoso
- CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal
| | - Marília I Figueira
- CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal
| | - Cátia V Vaz
- CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal
| | - Sílvia Socorro
- CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
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Amrutha NA, Archana PR, Mohan SG, Anto RJ, Sadasivan C. Pyridine derivatives as anticancer lead compounds with Fatty Acid Synthase as the target: An in silico-guided in vitro study. J Cell Biochem 2019; 120:16643-16657. [PMID: 31095793 DOI: 10.1002/jcb.28923] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2018] [Revised: 02/28/2019] [Accepted: 03/15/2019] [Indexed: 11/08/2022]
Abstract
For the past few decades, structure-based drug discovery (SBDD) has become an inevitable technique in the drug development process for screening hit compounds against therapeutic targets. Here, we have successfully used the SBDD approach viz. virtual high-throughput screening to identify potential inhibitors against the Ketoacyl synthase (KS) domain of Fatty acid synthase (FASN). Overexpression of FASN, and subsequent enhancement of de novo lipogenesis is a key survival strategy of cancer cells. Hence, targeting lipid metabolism using FASN inhibitors has been considered as a promising method to induce metabolic stress, thereby posing a survival disadvantage to cancer cells. In the present study, we have successfully identified eight FASN inhibitors from Asinex Elite database by implementing in silico tools. Five of the hit compounds share a common ring structure, which enables characteristic binding interactions with FASN-KS. Among them, in vitro validation showed that SFA 22637550 possesses significant FASN inhibitory activity and antiproliferative effect in human cancer cells of various origins. The maximum sensitivity was exhibited towards HepG2 hepatocellular carcinoma cells (IC50 = 28 µM). The mode of cell death was found to be apoptosis with a significant increase in SubG0 population without affecting any other phases of the cell cycle. The current study puts forward an excellent core structure for the development of potent FASN inhibitors for successfully targeting cancer cell metabolism, thereby causing selective cell death.
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Affiliation(s)
- Nisthul A Amrutha
- Department of Biotechnology and Microbiology, Kannur University, Thalassery Campus, Kannur, 670661, Kerala, India
| | - P Retnakumari Archana
- Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, 695014, Kerala, India
| | - Shankar G Mohan
- Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, 695014, Kerala, India
| | - Ruby John Anto
- Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, 695014, Kerala, India
| | - C Sadasivan
- Department of Biotechnology and Microbiology, Kannur University, Thalassery Campus, Kannur, 670661, Kerala, India
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Meng XH, Li N, Zhu HT, Wang D, Yang CR, Zhang YJ. Plant Resources, Chemical Constituents, and Bioactivities of Tea Plants from the Genus Camellia Section Thea. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2019; 67:5318-5349. [PMID: 30449099 DOI: 10.1021/acs.jafc.8b05037] [Citation(s) in RCA: 73] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/23/2023]
Abstract
Tea, as one of the most popular beverages with various bioactivities, is commonly produced from the fresh leaves of two widely cultivated tea plants, Camellia sinensis and C. sinensis var. assamica. Both plants belong to the genus Camellia section Thea, which was considered to have 12 species and 6 varieties according to Min's taxonomic system. Most species, except the cultivated species, are known as wild tea plants and have been exploited and utilized to produce tea by the local people of its growing areas. Thus far, six species and varieties have been phytochemically studied, leading to the identification of 398 compounds, including hydrolyzable tannins, flavan-3-ols, flavonoids, terpenoids, alkaloids, and other phenolic and related compounds. Various beneficial health effects were reported for tea and its components, involving antioxidant, antitumor, antimutagenic, antidiabetic, hypolipidemic, anti-inflammatory, antimicrobial, antiviral, antifungal, neuroprotective, hepatoprotective, etc. In this review, the geographical distribution of tea plants and the chemical constituents (1-398) reported from the genus Camellia section Thea and some tea products (green, black, oolong, and pu-erh tea) that have ever been studied between 1970 and 2018 have been summarized, taking species as the main hint, and the main biological activities are also discussed.
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Affiliation(s)
- Xiu-Hua Meng
- State Key Laboratory of Phytochemistry and Plant Resources of West China, Kunming Institute of Botany , Chinese Academy of Sciences , Kunming , Yunnan 650201 , People's Republic of China
- University of Chinese Academy of Sciences , Beijing 100049 , People's Republic of China
| | - Na Li
- State Key Laboratory of Phytochemistry and Plant Resources of West China, Kunming Institute of Botany , Chinese Academy of Sciences , Kunming , Yunnan 650201 , People's Republic of China
- University of Chinese Academy of Sciences , Beijing 100049 , People's Republic of China
| | - Hong-Tao Zhu
- State Key Laboratory of Phytochemistry and Plant Resources of West China, Kunming Institute of Botany , Chinese Academy of Sciences , Kunming , Yunnan 650201 , People's Republic of China
| | - Dong Wang
- State Key Laboratory of Phytochemistry and Plant Resources of West China, Kunming Institute of Botany , Chinese Academy of Sciences , Kunming , Yunnan 650201 , People's Republic of China
| | - Chong-Ren Yang
- State Key Laboratory of Phytochemistry and Plant Resources of West China, Kunming Institute of Botany , Chinese Academy of Sciences , Kunming , Yunnan 650201 , People's Republic of China
| | - Ying-Jun Zhang
- State Key Laboratory of Phytochemistry and Plant Resources of West China, Kunming Institute of Botany , Chinese Academy of Sciences , Kunming , Yunnan 650201 , People's Republic of China
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Niazvand F, Orazizadeh M, Khorsandi L, Abbaspour M, Mansouri E, Khodadadi A. Effects of Quercetin-Loaded Nanoparticles on MCF-7 Human Breast Cancer Cells. ACTA ACUST UNITED AC 2019; 55:medicina55040114. [PMID: 31013662 PMCID: PMC6524048 DOI: 10.3390/medicina55040114] [Citation(s) in RCA: 72] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2019] [Revised: 02/15/2019] [Accepted: 04/16/2019] [Indexed: 12/27/2022]
Abstract
Background and objectives: Previous studies have shown anti-tumor activity of quercetin (QT). However, the low bioavailability of QT has restricted its use. This study aimed to assess the toxic effect of QT encapsulated in solid lipid nanoparticles (QT-SLNs) on the growth of MCF-7 human breast cancer cells. Materials and Methods: MCF-7 and MCF-10A (non-tumorigenic cell line) cell lines treated with 25 µmol/mL of QT or QT-SLNs for 48 h. Cell viability, colony formation, oxidative stress, and apoptosis were evaluated to determine the toxic effects of the QT-SLNs. Results: The QT-SLNs with appropriate characteristics (particle size of 85.5 nm, a zeta potential of −22.5 and encapsulation efficiency of 97.6%) were prepared. The QT-SLNs showed sustained QT release until 48 h. Cytotoxicity assessments indicated that QT-SLNs inhibited MCF-7 cells growth with a low IC50 (50% inhibitory concentration) value, compared to the free QT. QT-SLNs induced a significant decrease in the viability and proliferation of MCF-7 cells, compared to the free QT. QT-SLN significantly increased reactive oxygen species (ROS) level and MDA contents and significantly decreased antioxidant enzyme activity in the MCF-7 cells. Following QT-SLNs treatment, the expression of the Bcl-2 protein significantly decreased, whereas Bx expression showed a significant increase in comparison with free QT-treated cells. Furthermore, The QT-SLNs significantly increased apoptotic and necrotic indexes in MCF-7 cells. Viability, proliferation, oxidative stress and apoptosis of MCF-10A cells were not affected by QT or QT-SLNs. Conclusions: According to the results of this study, SLN significantly enhanced the toxic effect of QT against human breast cancer cells.
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Affiliation(s)
- Firoozeh Niazvand
- Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
- Department of Anatomical Sciences, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | - Mahmoud Orazizadeh
- Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
- Department of Anatomical Sciences, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | - Layasadat Khorsandi
- Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
- Department of Anatomical Sciences, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | - Mohammadreza Abbaspour
- Targeted Drug Delivery Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Esrafil Mansouri
- Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
- Department of Anatomical Sciences, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | - Ali Khodadadi
- Cancer Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
- Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
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Abstract
Extracts from Cannabis species have aided the discovery of the endocannabinoid signaling system (ECSS) and phytocannabinoids that possess broad therapeutic potential. Whereas the reinforcing effects of C. sativa are largely attributed to CB1 receptor agonism by Δ9-tetrahydrocannabinol (Δ9-THC), the observed medicinal effects of Cannabis arise from the combined actions of various compounds. In addition to compounds bearing a classical cannabinoid structure, naturally occurring fatty acid amides and esters resembling anandamide and 2-arachidonoyl glycerol isolated from non- Cannabis species are also valuable tools for studying ECSS function. This review highlights the potential of plant-based secondary metabolites from Cannabis and unrelated species as ECSS modulators.
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Affiliation(s)
- Christopher W Cunningham
- Department of Pharmaceutical Sciences , Concordia University Wisconsin , Mequon , Wisconsin 53097 , United States
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Vemuri SK, Banala RR, Subbaiah G, Srivastava SK, Reddy AG, Malarvili T. Anti-cancer potential of a mix of natural extracts of turmeric, ginger and garlic: A cell-based study. ACTA ACUST UNITED AC 2019. [DOI: 10.1016/j.ejbas.2017.07.005] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- Satish Kumar Vemuri
- Smart Medical Academic and Research Training (SMART), Sunshine Hospitals, Secunderabad, Telangana, India
- Rajah Serfoji Government College, Thanjavur, Tamil Nadu, India
| | - Rajkiran Reddy Banala
- Smart Medical Academic and Research Training (SMART), Sunshine Hospitals, Secunderabad, Telangana, India
| | - G.P.V. Subbaiah
- Smart Medical Academic and Research Training (SMART), Sunshine Hospitals, Secunderabad, Telangana, India
| | - Saurabh Kumar Srivastava
- Smart Medical Academic and Research Training (SMART), Sunshine Hospitals, Secunderabad, Telangana, India
| | - A.V. Gurava Reddy
- Smart Medical Academic and Research Training (SMART), Sunshine Hospitals, Secunderabad, Telangana, India
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Çoban EA, Tecimel D, Şahin F, Deniz AAH. Targeting Cancer Metabolism and Cell Cycle by Plant-Derived Compounds. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1247:125-134. [DOI: 10.1007/5584_2019_449] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Guerra AR, Duarte MF, Duarte IF. Targeting Tumor Metabolism with Plant-Derived Natural Products: Emerging Trends in Cancer Therapy. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2018; 66:10663-10685. [PMID: 30227704 DOI: 10.1021/acs.jafc.8b04104] [Citation(s) in RCA: 66] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Recognition of neoplastic metabolic reprogramming as one of cancer's hallmarks has paved the way for developing novel metabolism-targeted therapeutic approaches. The use of plant-derived natural bioactive compounds for this endeavor is especially promising, due to their diverse structures and multiple targets. Hence, over the past decade, a growing number of studies have assessed the impact of phytochemicals on tumor cell metabolism, aiming at improving current knowledge on their mechanisms of action and, at the same time, evaluating their potential as anti-cancer metabolic modulators. In this Review, we focus on three classes of plant-derived compounds with promising anti-cancer activity-phenolic compounds, isoprenoids, and alkaloids-to describe their effects on major energetic and biosynthetic pathways of human tumor cells. Such a comprehensive and integrated account of the ability of these compounds to hit different metabolic targets is expected to contribute to the rational design and critical assessment of novel anti-cancer therapies based on natural-product-mediated metabolic reprogramming.
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Affiliation(s)
- Angela R Guerra
- Centro de Biotecnologia Agrícola e Agro-Alimentar do Alentejo (CEBAL), Instituto Politécnico de Beja , Apartado 6158 , 7801-908 Beja , Portugal
- CICECO - Instituto de Materiais de Aveiro, Departamento de Quı́mica , Universidade de Aveiro , Campus de Santiago , 3810-193 Aveiro , Portugal
| | - Maria F Duarte
- Centro de Biotecnologia Agrícola e Agro-Alimentar do Alentejo (CEBAL), Instituto Politécnico de Beja , Apartado 6158 , 7801-908 Beja , Portugal
- ICAAM - Instituto de Ciências Agrárias e Ambientais Mediterrânicas , Universidade de Évora , Pólo da Mitra, 7006-554 Évora , Portugal
| | - Iola F Duarte
- CICECO - Instituto de Materiais de Aveiro, Departamento de Quı́mica , Universidade de Aveiro , Campus de Santiago , 3810-193 Aveiro , Portugal
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Tungmunnithum D, Thongboonyou A, Pholboon A, Yangsabai A. Flavonoids and Other Phenolic Compounds from Medicinal Plants for Pharmaceutical and Medical Aspects: An Overview. MEDICINES (BASEL, SWITZERLAND) 2018; 5:E93. [PMID: 30149600 PMCID: PMC6165118 DOI: 10.3390/medicines5030093] [Citation(s) in RCA: 734] [Impact Index Per Article: 104.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Revised: 08/20/2018] [Accepted: 08/22/2018] [Indexed: 12/11/2022]
Abstract
Phenolic compounds as well as flavonoids are well-known as antioxidant and many other important bioactive agents that have long been interested due to their benefits for human health, curing and preventing many diseases. This review attempts to demonstrate an overview of flavonoids and other phenolic compounds as the interesting alternative sources for pharmaceutical and medicinal applications. The examples of these phytochemicals from several medicinal plants are also illustrated, and their potential applications in pharmaceutical and medical aspects, especially for health promoting e.g., antioxidant effects, antibacterial effect, anti-cancer effect, cardioprotective effects, immune system promoting and anti-inflammatory effects, skin protective effect from UV radiation and so forth are highlighted.
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Affiliation(s)
- Duangjai Tungmunnithum
- Department of Pharmaceutical Botany, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.
- Department of Botany, Tsukuba Botanical Garden, National Museum of Nature and Science, 4-1-1 Amakubo, Tsukuba 305-0005, Japan.
| | - Areeya Thongboonyou
- Department of Pharmaceutical Botany, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.
| | - Apinan Pholboon
- Department of Pharmaceutical Botany, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.
| | - Aujana Yangsabai
- Department of Pharmaceutical Botany, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.
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Menendez JA, Lupu R. Fatty acid synthase (FASN) as a therapeutic target in breast cancer. Expert Opin Ther Targets 2017; 21:1001-1016. [PMID: 28922023 DOI: 10.1080/14728222.2017.1381087] [Citation(s) in RCA: 198] [Impact Index Per Article: 24.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Ten years ago, we put forward the metabolo-oncogenic nature of fatty acid synthase (FASN) in breast cancer. Since the conception of this hypothesis, which provided a model to explain how FASN is intertwined with various signaling networks to cell-autonomously regulate breast cancer initiation and progression, FASN has received considerable attention as a therapeutic target. However, despite the ever-growing evidence demonstrating the involvement of FASN as part of the cancer-associated metabolic reprogramming, translation of the basic science-discovery aspects of FASN blockade to the clinical arena remains a challenge. Areas covered: Ten years later, we herein review the preclinical lessons learned from the pharmaceutical liabilities of the first generation of FASN inhibitors. We provide an updated view of the current development and clinical testing of next generation FASN-targeted drugs. We also discuss new clinico-molecular approaches that should help us to convert roadblocks into roadways that will propel forward our therapeutic understanding of FASN. Expert opinion: With the recent demonstration of target engagement and early signs of clinical activity with the first orally available, selective, potent and reversible FASN inhibitor, we can expect Big pharma to revitalize their interest in lipogenic enzymes as well-credentialed targets for oncology drug development in breast cancer.
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Affiliation(s)
- Javier A Menendez
- a ProCURE (Program Against Cancer Therapeutic Resistance) , Metabolism & Cancer Group, Catalan Institute of Oncology , Girona , Spain.,b Girona Biomedical Research Institute (IDIBGI) , Parc Hospitalari Martí i Julià , Girona , Spain
| | - Ruth Lupu
- c Department of Medicine and Experimental Pathology , Mayo Clinic , Rochester , MN , USA.,d Mayo Clinic Cancer Center , Rochester , MN , USA
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Arlia-Ciommo A, Svistkova V, Mohtashami S, Titorenko VI. A novel approach to the discovery of anti-tumor pharmaceuticals: searching for activators of liponecrosis. Oncotarget 2017; 7:5204-25. [PMID: 26636650 PMCID: PMC4868681 DOI: 10.18632/oncotarget.6440] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2015] [Accepted: 11/21/2015] [Indexed: 02/04/2023] Open
Abstract
A recently conducted chemical genetic screen for pharmaceuticals that can extend longevity of the yeast Saccharomyces cerevisiae has identified lithocholic acid as a potent anti-aging molecule. It was found that this hydrophobic bile acid is also a selective anti-tumor chemical compound; it kills different types of cultured cancer cells if used at concentrations that do not compromise the viability of non-cancerous cells. These studies have revealed that yeast can be successfully used as a model organism for high-throughput screens aimed at the discovery of selectively acting anti-tumor small molecules. Two metabolic traits of rapidly proliferating fermenting yeast, namely aerobic glycolysis and lipogenesis, are known to be similar to those of cancer cells. The mechanisms underlying these key metabolic features of cancer cells and fermenting yeast have been established; such mechanisms are discussed in this review. We also suggest how a yeast-based chemical genetic screen can be used for the high-throughput development of selective anti-tumor pharmaceuticals that kill only cancer cells. This screen consists of searching for chemical compounds capable of increasing the abundance of membrane lipids enriched in unsaturated fatty acids that would therefore be toxic only to rapidly proliferating cells, such as cancer cells and fermenting yeast.
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Affiliation(s)
| | | | - Sadaf Mohtashami
- Department of Biology, Concordia University, Montreal, Quebec, Canada
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Shankar E, Montellano J, Gupta S. Chapter 5 Green Tea Polyphenols in the Prevention and Therapy of Prostate Cancer. TRADITIONAL HERBAL MEDICINES FOR MODERN TIMES 2016. [DOI: 10.1201/9781315370156-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Zhang Z, Garzotto M, Beer TM, Thuillier P, Lieberman S, Mori M, Stoller WA, Farris PE, Shannon J. Effects of ω-3 Fatty Acids and Catechins on Fatty Acid Synthase in the Prostate: A Randomized Controlled Trial. Nutr Cancer 2016; 68:1309-1319. [PMID: 27646578 DOI: 10.1080/01635581.2016.1224365] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Animal and human studies suggest fish oil and green tea may have protective effect on prostate cancer. Fatty acid synthase (FAS) has been hypothesized to be linked to chemoprotective effects of both compounds. This study evaluated the independent and joint effects of fish oil (FO) and green tea supplement (epigallocatechin-3-gallate, EGCG) on FAS and Ki-67 levels in prostate tissue. Through a double-blinded, randomized controlled trial with 2 × 2 factorial design, 89 men scheduled for repeat prostate biopsy following an initial negative prostate biopsy were randomized into either FO alone (1.9 g DHA + EPA/day), EGCG alone (600 mg/day), a combination of FO and EGCG, or placebo. We used linear mixed-effects models to test the differences of prostate tissue FAS and Ki-67 by immunohistochemistry between pre- and post-intervention within each group, as well as between treatment groups. Results did not show significant difference among treatment groups in pre-to-post-intervention changes of FAS (P = 0.69) or Ki-67 (P = 0.26). Comparing placebo group with any of the treatment groups, we did not find significant difference in FAS or Ki-67 changes (all P > 0.05). Results indicate FO or EGCG supplementation for a short duration may not be sufficient to produce biologically meaningful changes in FAS or Ki-67 levels in prostate tissue.
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Affiliation(s)
- Zhenzhen Zhang
- a OHSU-PSU School of Public Health, Oregon Health and Science University , Portland , Oregon , USA
| | - Mark Garzotto
- b Department of Urology , Portland Veterans Administration Medical Center, Oregon Health and Science University , Portland , Oregon , USA
| | - Tomasz M Beer
- c Knight Cancer Institute, Oregon Health and Science University , Portland , Oregon , USA
| | - Philippe Thuillier
- a OHSU-PSU School of Public Health, Oregon Health and Science University , Portland , Oregon , USA.,c Knight Cancer Institute, Oregon Health and Science University , Portland , Oregon , USA.,d Department of Dermatology , Oregon Health and Science University , Portland , Oregon , USA
| | - Stephen Lieberman
- e Department of Urology , Kaiser Permanente Northwest , Clackamas , Oregon , USA
| | - Motomi Mori
- a OHSU-PSU School of Public Health, Oregon Health and Science University , Portland , Oregon , USA.,c Knight Cancer Institute, Oregon Health and Science University , Portland , Oregon , USA
| | - Wesley A Stoller
- a OHSU-PSU School of Public Health, Oregon Health and Science University , Portland , Oregon , USA
| | - Paige E Farris
- a OHSU-PSU School of Public Health, Oregon Health and Science University , Portland , Oregon , USA
| | - Jackilen Shannon
- a OHSU-PSU School of Public Health, Oregon Health and Science University , Portland , Oregon , USA
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Chinese Herbs Interfering with Cancer Reprogramming Metabolism. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2016; 2016:9282813. [PMID: 27242914 PMCID: PMC4875995 DOI: 10.1155/2016/9282813] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/06/2015] [Accepted: 02/03/2016] [Indexed: 12/11/2022]
Abstract
Emerging evidence promotes a reassessment of metabolic reprogramming regulation in cancer research. Although there exists a long history of Chinese herbs applied in cancer treatment, few reports have addressed the effects of Chinese herbal components on metabolic reprogramming, which is a central cancer hallmark involved in the slowing or prevention of chemoresistance in cancer cells. In this review, we have focused on four core elements altered by metabolic reprogramming in cancer cells. These include glucose transport, glycolysis, mitochondrial oxidative phosphorylation, and fatty acid synthesis. With this focus, we have summarized recent advances in metabolic reprogramming of cancer cells in response to specific Chinese herbal components. We propose that exploring Chinese herbal interference in cancer metabolic reprogramming might identify new therapeutic targets for cancer and more ways in which to approach metabolism-related diseases.
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FAN HUIJIN, LIANG YAN, JIANG BING, LI XIABING, XUN HANG, SUN JIA, HE WEI, LAU HAYTONG, MA XIAOFENG. Curcumin inhibits intracellular fatty acid synthase and induces apoptosis in human breast cancer MDA-MB-231 cells. Oncol Rep 2016; 35:2651-6. [DOI: 10.3892/or.2016.4682] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2015] [Accepted: 10/06/2015] [Indexed: 11/05/2022] Open
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Chowdhury A, Sarkar J, Chakraborti T, Pramanik PK, Chakraborti S. Protective role of epigallocatechin-3-gallate in health and disease: A perspective. Biomed Pharmacother 2016; 78:50-59. [DOI: 10.1016/j.biopha.2015.12.013] [Citation(s) in RCA: 92] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2015] [Revised: 12/03/2015] [Accepted: 12/15/2015] [Indexed: 12/28/2022] Open
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Mullen GE, Yet L. Progress in the development of fatty acid synthase inhibitors as anticancer targets. Bioorg Med Chem Lett 2015; 25:4363-9. [DOI: 10.1016/j.bmcl.2015.08.087] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2015] [Revised: 08/26/2015] [Accepted: 08/31/2015] [Indexed: 12/20/2022]
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