|
1
|
Casarcia N, Rogers P, Guld E, Iyer S, Li Y, Burcher JT, DeLiberto LK, Banerjee S, Bishayee A. Phytochemicals for the prevention and treatment of pancreatic cancer: Current progress and future prospects. Br J Pharmacol 2025; 182:2181-2234. [PMID: 37740585 DOI: 10.1111/bph.16249] [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: 06/26/2023] [Revised: 09/06/2023] [Accepted: 09/13/2023] [Indexed: 09/24/2023] Open
Abstract
Pancreatic cancer is the third leading cause of cancer-related deaths in the United States, owing to its aggressive nature and suboptimal treatment options, emphasizing the need for novel therapeutic approaches. Emerging studies have exhibited promising results regarding the therapeutic utility of plant-derived compounds (phytochemicals) in pancreatic cancer. The purpose of this review is to evaluate the potential of phytochemicals in the treatment and prevention of pancreatic cancer. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses was applied to collect articles for this review. Scholarly databases, including PubMed, Scopus and ScienceDirect, were queried for relevant studies using the following keywords: phytochemicals, phenolics, terpenoids, alkaloids, sulfur-containing compounds, in vitro, in vivo, clinical studies, pancreatic cancer, tumour, treatment and prevention. Aggregate results pooled from qualified studies indicate phytochemicals can inhibit pancreatic cancer cell growth or decrease tumour size and volume in animal models. These effects have been attributed to various mechanisms, such as increasing proapoptotic factors, decreasing antiapoptotic factors, or inducing cell death and cell cycle arrest. Notable signalling pathways modulated by phytochemicals include the rat sarcoma/mitogen activated protein kinase, wingless-related integration site/β-catenin and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signal transduction pathways. Clinically, phytochemicals have been found to increase survival while being well-tolerated and safe, though research is scarce. While these promising results have produced great interest in this field, further in-depth studies are required to characterize the anticancer activities of phytochemicals before they can be utilized to prevent or treat pancreatic cancer in clinical practice. LINKED ARTICLES: This article is part of a themed issue Natural Products and Cancer: From Drug Discovery to Prevention and Therapy. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v182.10/issuetoc.
Collapse
Affiliation(s)
- Nicolette Casarcia
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
| | - Patrick Rogers
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
| | - Emma Guld
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
| | - Samvit Iyer
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
| | - Yutong Li
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
| | - Jack T Burcher
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
| | - Lindsay K DeLiberto
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
| | - Sabyasachi Banerjee
- Department of Pharmaceutical Chemistry, Gupta College of Technological Sciences, Asansol, India
| | - Anupam Bishayee
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
| |
Collapse
|
|
2
|
Nonsuwan P, Niwetbowornchai N, Insawang K, Kunwong N, Srichan K, Srisawat C, Dana P, Saengkrit N, Nguyen KT, Punnakitikashem P. Synergistic anticancer activity of resveratrol-loaded polymeric nanoparticles and sunitinib in colorectal cancer treatment. ROYAL SOCIETY OPEN SCIENCE 2025; 12:241817. [PMID: 40271141 PMCID: PMC12014242 DOI: 10.1098/rsos.241817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Revised: 03/18/2025] [Accepted: 03/19/2025] [Indexed: 04/25/2025]
Abstract
The development of novel and effective treatment strategies, particularly through drug combinations, can significantly enhance therapeutic outcomes. This study explores the innovative combination of resveratrol (RES), a phenolic compound, with sunitinib (SUNI), a multitarget tyrosine kinase inhibitor, for targeting human colon adenocarcinoma cell line HT-29. We identified a synergistic effect at a SUNI:RES ratio of 1:8, based on their half-maximal inhibitory concentration values. Increasing the dosage of the combined treatment led to a notable reduction in cell viability, observed in both two-dimensional (2D) and three-dimensional cell cultures. To improve RES therapeutic efficacy, drug-loaded polymeric nanoparticles (PLGA-RES) were successfully fabricated with an average diameter of 178.4 ± 4.6 nm. The combination of PLGA-RES and free SUNI at the optimal ratio exhibited enhanced anticancer activity, reducing cell viability by approximately 25 and 15% more than PLGA-RES and free SUNI alone, respectively, in 2D cultures. Moreover, this combination therapy demonstrated superior effectiveness in treating HT-29 spheroids over 24 and 48 h. These findings highlight the potential of this combined approach to improve colorectal cancer treatment outcomes.
Collapse
Affiliation(s)
- Punnida Nonsuwan
- Department of Biochemistry, Mahidol University Faculty of Medicine Siriraj Hospital, Bangkok10700, Thailand
- Siriraj Center of Research Excellence in Theranostic Nanomedicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Nattarika Niwetbowornchai
- Department of Biochemistry, Mahidol University Faculty of Medicine Siriraj Hospital, Bangkok10700, Thailand
| | - Kanyanut Insawang
- Department of Biochemistry, Mahidol University Faculty of Medicine Siriraj Hospital, Bangkok10700, Thailand
| | - Natsuda Kunwong
- Department of Biochemistry, Mahidol University Faculty of Medicine Siriraj Hospital, Bangkok10700, Thailand
| | - Kornrawee Srichan
- Department of Biochemistry, Mahidol University Faculty of Medicine Siriraj Hospital, Bangkok10700, Thailand
| | - Chatchawan Srisawat
- Department of Biochemistry, Mahidol University Faculty of Medicine Siriraj Hospital, Bangkok10700, Thailand
- Siriraj Center of Research Excellence in Theranostic Nanomedicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Paweena Dana
- National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani12120, Thailand
| | - Nattika Saengkrit
- National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani12120, Thailand
| | - Kytai T. Nguyen
- Department of Bioengineering, University of Texas at Arlington, Arlington, TX76019, USA
| | - Primana Punnakitikashem
- Department of Biochemistry, Mahidol University Faculty of Medicine Siriraj Hospital, Bangkok10700, Thailand
- Siriraj Center of Research Excellence in Theranostic Nanomedicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| |
Collapse
|
|
3
|
Vlasova O, Antonova I, Magomedova K, Osipova A, Shtompel P, Borunova A, Zabotina T, Belitsky G, Budunova I, Jordan A, Kirsanov K, Yakubovskaya M. Anticancer Plant Secondary Metabolites Evicting Linker Histone H1.2 from Chromatin Activate Type I Interferon Signaling. Int J Mol Sci 2025; 26:375. [PMID: 39796235 PMCID: PMC11722331 DOI: 10.3390/ijms26010375] [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: 10/18/2024] [Revised: 12/03/2024] [Accepted: 12/04/2024] [Indexed: 01/13/2025] Open
Abstract
Previously we discovered that among 15 DNA-binding plant secondary metabolites (PSMs) possessing anticancer activity, 11 compounds cause depletion of the chromatin-bound linker histones H1.2 and/or H1.4. Chromatin remodeling or multiH1 knocking-down is known to promote the upregulation of repetitive elements, ultimately triggering an interferon (IFN) response. Herein, using HeLa cells and applying fluorescent reporter assay with flow cytometry, immunofluorescence staining and quantitative RT-PCR, we studied effects of PSMs both evicting linker histones from chromatin and not influencing their location in nucleus. We found that (1) 8 PSMs, evicting linker histone H1.2 from chromatin, activated significantly the type I IFN signaling pathway and out of these compounds resveratrol, berberine, genistein, delphinidin, naringenin and curcumin also caused LINE1 expression. Fisetin and quercetin, which also induced linker histone H1.2 eviction from chromatin, significantly activated only type I IFN signaling, but not LINE1 expression; (2) curcumin, sanguinarine and kaempferol, causing significant depletion of the chromatin-bound linker histone H1.4 but not significantly influencing H1.2 presence in chromatin, activate type I IFN signaling less intensively without any changes in LINE1 expression; (3) four PSMs, which did not cause linker histone eviction, displayed neither IFN signaling activation nor enhancement of LINE1 expression. Thus, we have shown for the first time that chromatin destabilization observed by depletion of chromatin-bound linker histone H1.2 caused by anticancer DNA-binding PSMs is accompanied by enhancement of type I IFN signaling, and that LINE1 expression often impacts this activation.
Collapse
Affiliation(s)
- Olga Vlasova
- N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia, 24 Kashirskoe Shosse, 115522 Moscow, Russia (K.M.)
| | - Irina Antonova
- N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia, 24 Kashirskoe Shosse, 115522 Moscow, Russia (K.M.)
| | - Khamis Magomedova
- N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia, 24 Kashirskoe Shosse, 115522 Moscow, Russia (K.M.)
| | - Alena Osipova
- N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia, 24 Kashirskoe Shosse, 115522 Moscow, Russia (K.M.)
- SBHI Moscow Clinical Scientific Center Named After Loginov MHD, 111123 Moscow, Russia
| | - Polina Shtompel
- N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia, 24 Kashirskoe Shosse, 115522 Moscow, Russia (K.M.)
| | - Anna Borunova
- N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia, 24 Kashirskoe Shosse, 115522 Moscow, Russia (K.M.)
| | - Tatiana Zabotina
- N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia, 24 Kashirskoe Shosse, 115522 Moscow, Russia (K.M.)
| | - Gennady Belitsky
- N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia, 24 Kashirskoe Shosse, 115522 Moscow, Russia (K.M.)
| | - Irina Budunova
- Department of Dermatology, Northwestern University, Chicago, IL 60611, USA
| | - Albert Jordan
- Institut de Biologia Molecular de Barcelona (IBMB-CSIC), 08028 Barcelona, Spain
| | - Kirill Kirsanov
- N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia, 24 Kashirskoe Shosse, 115522 Moscow, Russia (K.M.)
- Institute of Medicine, Peoples’ Friendship University of Russia (RUDN University), Miklukho-Maklaya St. 6, 117198 Moscow, Russia
| | - Marianna Yakubovskaya
- N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia, 24 Kashirskoe Shosse, 115522 Moscow, Russia (K.M.)
| |
Collapse
|
|
4
|
Godiyal Y, Maheshwari D, Taniguchi H, Zinzuwadia SS, Morera-Díaz Y, Tewari D, Bishayee A. Role of PD-1/PD-L1 signaling axis in oncogenesis and its targeting by bioactive natural compounds for cancer immunotherapy. Mil Med Res 2024; 11:82. [PMID: 39690423 DOI: 10.1186/s40779-024-00586-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Accepted: 11/29/2024] [Indexed: 12/19/2024] Open
Abstract
Cancer is a global health problem and one of the leading causes of mortality. Immune checkpoint inhibitors have revolutionized the field of oncology, emerging as a powerful treatment strategy. A key pathway that has garnered considerable attention is programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1). The interaction between PD-L1 expressed on tumor cells and PD-1 reduces the innate immune response and thus compromises the capability of the body's immune system. Furthermore, it controls the phenotype and functionality of innate and adaptive immune components. A range of monoclonal antibodies, including avelumab, atezolizumab, camrelizumab, dostarlimab, durvalumab, sinitilimab, toripalimab, and zimberelimab, have been developed for targeting the interaction between PD-1 and PD-L1. These agents can induce a broad spectrum of autoimmune-like complications that may affect any organ system. Recent studies have focused on the effect of various natural compounds that inhibit immune checkpoints. This could contribute to the existing arsenal of anticancer drugs. Several bioactive natural agents have been shown to affect the PD-1/PD-L1 signaling axis, promoting tumor cell apoptosis, influencing cell proliferation, and eventually leading to tumor cell death and inhibiting cancer progression. However, there is a substantial knowledge gap regarding the role of different natural compounds targeting PD-1 in the context of cancer. Hence, this review aims to provide a common connection between PD-1/PD-L1 blockade and the anticancer effects of distinct natural molecules. Moreover, the primary focus will be on the underlying mechanism of action as well as the clinical efficacy of bioactive molecules. Current challenges along with the scope of future research directions targeting PD-1/PD-L1 interactions through natural substances are also discussed.
Collapse
Affiliation(s)
- Yogesh Godiyal
- Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, New Delhi, 110017, India
| | - Drishti Maheshwari
- Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, New Delhi, 110017, India
| | - Hiroaki Taniguchi
- Department of Experimental Embryology, Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences, Jastrzebiec, 05-552, Magdalenka, Poland
- African Genome Center, Mohammed VI Polytechnic University, Hay Moulay Rachid, 43150, Ben Guerir, Morocco
| | - Shweta S Zinzuwadia
- Department of Pharmacology, College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL, 34211, USA
| | - Yanelys Morera-Díaz
- Clinical Investigation and Biomedical Research Directions, Center for Genetic Engineering and Biotechnology, 11600, Havana, Cuba
| | - Devesh Tewari
- Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, New Delhi, 110017, India.
| | - Anupam Bishayee
- Department of Pharmacology, College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL, 34211, USA.
| |
Collapse
|
|
5
|
Ronghe R, Tavares AAS. The skeleton: an overlooked regulator of systemic glucose metabolism in cancer? Front Oncol 2024; 14:1481241. [PMID: 39588310 PMCID: PMC11586348 DOI: 10.3389/fonc.2024.1481241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Accepted: 10/22/2024] [Indexed: 11/27/2024] Open
Abstract
Recent discoveries demonstrated the skeleton's role as an endocrine organ regulating whole-body glucose homeostasis. Glucose metabolism is critical for rapid cell proliferation and tumour growth through increasing glucose uptake and fermentation of glucose to lactate despite being in an aerobic environment. This hypothesis paper discusses emerging evidence on how bones can regulate whole-body glucose homeostasis with potential to impact on tumour growth and proliferation. Moreover, it proposes a clinical link between bone glucose metabolism and prognosis of cancer based on recent clinical trial data. Targeting metabolic pathways related with classic glucose metabolism and also bone metabolism, novel methods of cancer therapy and treatment could be developed. This paper objective is to highlight the need for future research on this altered metabolism with potential to change future management of cancer patients.
Collapse
Affiliation(s)
- Rucha Ronghe
- Edinburgh Medical School, The University of Edinburgh, Edinburgh, United Kingdom
| | - Adriana A. S. Tavares
- University/British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh, Queens Medical Research Institute, Edinburgh, United Kingdom
- Edinburgh Imaging, The University of Edinburgh, Queens Medical Research Institute, Edinburgh, United Kingdom
| |
Collapse
|
|
6
|
Fakhri S, Moradi SZ, Moradi SY, Piri S, Shiri Varnamkhasti B, Piri S, Khirehgesh MR, Bishayee A, Casarcia N, Bishayee A. Phytochemicals regulate cancer metabolism through modulation of the AMPK/PGC-1α signaling pathway. BMC Cancer 2024; 24:1079. [PMID: 39223494 PMCID: PMC11368033 DOI: 10.1186/s12885-024-12715-7] [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: 03/12/2024] [Accepted: 07/26/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND Due to the complex pathophysiological mechanisms involved in cancer progression and metastasis, current therapeutic approaches lack efficacy and have significant adverse effects. Therefore, it is essential to establish novel strategies for combating cancer. Phytochemicals, which possess multiple biological activities, such as antioxidant, anti-inflammatory, antimutagenic, immunomodulatory, antiproliferative, anti-angiogenesis, and antimetastatic properties, can regulate cancer progression and interfere in various stages of cancer development by suppressing various signaling pathways. METHODS The current systematic and comprehensive review was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) criteria, using electronic databases, including PubMed, Scopus, and Science Direct, until the end of December 2023. After excluding unrelated articles, 111 related articles were included in this systematic review. RESULTS In this current review, the major signaling pathways of cancer metabolism are highlighted with the promising anticancer role of phytochemicals. This was through their ability to regulate the AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) signaling pathway. The AMPK/PGC-1α signaling pathway plays a crucial role in cancer cell metabolism via targeting energy homeostasis and mitochondria biogenesis, glucose oxidation, and fatty acid oxidation, thereby generating ATP for cell growth. As a result, targeting this signaling pathway may represent a novel approach to cancer treatment. Accordingly, alkaloids, phenolic compounds, terpene/terpenoids, and miscellaneous phytochemicals have been introduced as promising anticancer agents by regulating the AMPK/PGC-1α signaling pathway. Novel delivery systems of phytochemicals targeting the AMPK/PGC-1α pathway in combating cancer are also highlighted in this review.
Collapse
Affiliation(s)
- Sajad Fakhri
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran.
| | - Seyed Zachariah Moradi
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran
| | - Seyed Yahya Moradi
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran
| | - Sarina Piri
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran
| | - Behrang Shiri Varnamkhasti
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran
| | - Sana Piri
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran
| | - Mohammad Reza Khirehgesh
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran
| | | | - Nicolette Casarcia
- Department of Pharmacology, College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL, 34211, USA
| | - Anupam Bishayee
- Department of Pharmacology, College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL, 34211, USA.
| |
Collapse
|
|
7
|
Abd Elhamid AS, Heikal L, Ghareeb DA, Abdulmalek SA, Mady O, Teleb M, Khattab SN, El-Gizawy SA. Engineering Thermo/pH-Responsive Lactoferrin Nanostructured Microbeads for Oral Targeting of Colorectal Cancer. ACS Biomater Sci Eng 2024; 10:4985-5000. [PMID: 39079030 DOI: 10.1021/acsbiomaterials.4c00666] [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] [Indexed: 08/13/2024]
Abstract
AIM Colorectal cancer is an extremely aggressive form of cancer that often leads to death. Lactoferrin shows potential for targeting and treating colorectal cancer; however, oral delivery faces hurdles hampering clinical applications. We engineered dual-responsive lactoferrin nanostructured microbeads to overcome delivery hurdles and enhance drug targeting. METHODS The hydrophobic drug mesalazine (MSZ) was coupled to lactoferrin to form amphiphilic conjugate nanoparticles, dispersed in water. The lipid-soluble polyphenolic drug resveratrol (RSV) was then encapsulated into the hydrophobic core of LF-MSZ nanoparticles. To impart thermoresponsive properties, the dual-payload NPs were coupled with a PNIPAAm shell; finally, to further endow the nanoparticles with gastrointestinal resistance and pH responsiveness, the nanoparticles were microencapsulated into ionically cross-linked pectin-alginate beads. RESULTS The nanoparticles showed enhanced internalization and cytotoxicity against HCT colon cancer cells via LF-receptor-mediated endocytosis. Thermal triggering and tuned release were conferred by the temperature-sensitive polymer. The coatings protected the drugs from degradation. Orally delivered microbeads significantly reduced tumor burden in a mouse colon cancer model, lowering carcinoembryonic antigen and elevating antioxidant enzymes. Apoptotic pathways were stimulated, indicated by heightened Bax/Bcl2 ratio and caspase-3/9 expression. CONCLUSION Overall, we propose the innovative lactoferrin nanostructured microbeads as a paradigm shift in oral colorectal cancer therapeutics.
Collapse
Affiliation(s)
- Ahmed S Abd Elhamid
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt
| | - Lamia Heikal
- Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt
| | - Doaa A Ghareeb
- Bio-screening and Preclinical Trial Lab, Biochemistry Department, Faculty of Science, Alexandria University, Alexandria 21511, Egypt
- Center of Excellence for Drug Preclinical Studies (CE-DPS), Pharmaceutical and Fermentation Industry Development Center, City of Scientific Research & Technological Applications, New Borg El Arab, Alexandria 21934, Egypt
| | - Shaymaa A Abdulmalek
- Bio-screening and Preclinical Trial Lab, Biochemistry Department, Faculty of Science, Alexandria University, Alexandria 21511, Egypt
- Center of Excellence for Drug Preclinical Studies (CE-DPS), Pharmaceutical and Fermentation Industry Development Center, City of Scientific Research & Technological Applications, New Borg El Arab, Alexandria 21934, Egypt
| | - Omar Mady
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt
| | - Mohamed Teleb
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt
| | - Sherine N Khattab
- Chemistry Department, Faculty of Science, Alexandria University, Alexandria 21321, Egypt
| | - Sanaa A El-Gizawy
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt
| |
Collapse
|
|
8
|
Sahu RK, Tandon S, Singh S, Das BC, Hedau ST. Methyl CpG binding protein MBD2 has a regulatory role on the BRCA1 gene expression and its modulation by resveratrol in ER+, PR+ & triple-negative breast cancer cells. BMC Cancer 2024; 24:566. [PMID: 38711004 PMCID: PMC11071212 DOI: 10.1186/s12885-024-12274-x] [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: 11/08/2023] [Accepted: 04/16/2024] [Indexed: 05/08/2024] Open
Abstract
BACKGROUND Resveratrol has demonstrated its ability to regulate BRCA1 gene expression in breast cancer cells, and previous studies have established the binding of MBD proteins to BRCA1 gene promoter regions. However, the molecular mechanism underlying these interactions remains to be elucidated. The aimed to evaluate the impact of MBD proteins on the regulation of BRCA1, BRCA2, and p16 genes and their consequential effects on breast cancer cells. METHODS Efficacy of resveratrol was assessed using the MTT assay. Binding interactions were investigated through EMSA, ChIP, & MeIP assay. Expression analyses of MBD genes and proteins were conducted using qRT-PCR and western blotting, respectively. Functional assays, including clonogenic, migratory, and sphere formation assays were used to assess cancer cells' colony-forming, metastatic, and tumor-forming abilities. The cytotoxicity of resveratrol on cancer cells was also tested using an apoptosis assay. RESULTS The study determined an IC50 of 30µM for resveratrol. MBD proteins were found to bind to the BRCA1 gene promoter. Resveratrol exhibited regulatory effects on MBD gene expression, subsequently impacting BRCA1 gene expression and protein levels. Higher concentrations of resveratrol resulted in reduced colony and sphere formation, decreases migration of cancer cells, and an increases number of apoptotic cells in breast cancer cells. Impact Identification of MBD2-BRCA1 axis indicates their significant role in the induction of apoptosis and reduction of metastasis and proliferation in breast cancer cells. Further therapy can be designed to target these MBD proteins and resveratrol could be used along with other anticancer drugs to target breast cancer. CONCLUSIONS In conclusion MBD2 protein interact to the BRCA1 gene promoter, and resveratrol modulates MBD2 gene expression, which in turn regulates BRCA1 gene expression, and inhibits cell proliferation, migration, and induces apoptosis in ER+, PR+ & Triple negative breast cancer cells.
Collapse
Affiliation(s)
- Ram Krishna Sahu
- Division of Molecular Oncology, ICMR-National Institute of Cancer Prevention and Research, I -7, Sector - 39, Noida, Uttar Pradesh, 201301, India
- Amity Institute of Molecular Medicine & Stem Cell Research, Amity University, Noida, Uttar Pradesh, 201313, India
| | | | - Shalini Singh
- Division of Clinical Oncology, ICMR-National Institute of Cancer Prevention and Research, I -7, Sector - 39, Noida, Uttar Pradesh, 201301, India
| | - Bhudev Chandra Das
- Amity Institute of Molecular Medicine & Stem Cell Research, Amity University, Noida, Uttar Pradesh, 201313, India
| | - Suresh T Hedau
- Division of Molecular Oncology, ICMR-National Institute of Cancer Prevention and Research, I -7, Sector - 39, Noida, Uttar Pradesh, 201301, India.
| |
Collapse
|
|
9
|
Fu Q, Lu Z, Chang Y, Jin T, Zhang M. Bibliometric and visualized analysis of resveratrol in anticancer investigations. Food Sci Nutr 2024; 12:2223-2239. [PMID: 38628201 PMCID: PMC11016421 DOI: 10.1002/fsn3.3932] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2023] [Revised: 12/17/2023] [Accepted: 12/19/2023] [Indexed: 04/19/2024] Open
Abstract
A growing number of publications have shown that resveratrol has anticancer effects and has become a hotspot in cancer research. The purpose of this study is to analyze the academic results and research trends in resveratrol within the field of anticancer and to predict the future trends in this field. We conducted a literature search for resveratrol in anticancer research from 2003 to 2022 using the Science Citation Index Expanded of the Web of Science Core Collection. The visualization software was used to perform the bibliometric analysis. A total of 1463 publications from 2003 to 2022 were retrieved. China had the highest number of publications. Taipei Medical University became the research institution with the largest number of publications worldwide. The journals with the highest output and co-citation frequency were Molecules and Cancer Research. Levenson, Anait S and Jaeger, Walter published the largest number of papers. Jang, MS was the most co-cited author. Timeline View shows trends and relationship between research topics over time and suggests that the emerging frontier of resveratrol in anticancer may be "resveratrol induces apoptosis." As more and more evidence shows the important role of resveratrol in anticancer, further research on its mechanisms and target discovery may become a major direction for future research. The bibliometric analysis findings of this study will significantly contribute to scholars' comprehensive understanding of the anticancer effects and mechanisms of action of resveratrol, aiding in delineating research hotspots and frontier directions within this field, thereby providing guidance for future investigations.
Collapse
Affiliation(s)
- Qiang Fu
- Department of Ultrasound MedicineAffiliated Hospital of Yanbian UniversityYanjiP. R. China
- Department of Pathology and Cancer Research CenterYanbian University Medical CollegeYanjiP. R. China
- Key Laboratory of the Science and Technology Department of Jilin ProvinceYanjiP. R. China
| | - Zhongqi Lu
- Department of Ultrasound MedicineAffiliated Hospital of Yanbian UniversityYanjiP. R. China
- Department of Pathology and Cancer Research CenterYanbian University Medical CollegeYanjiP. R. China
- Key Laboratory of the Science and Technology Department of Jilin ProvinceYanjiP. R. China
| | - Ying Chang
- Department of Ultrasound MedicineAffiliated Hospital of Yanbian UniversityYanjiP. R. China
- Department of Pathology and Cancer Research CenterYanbian University Medical CollegeYanjiP. R. China
- Key Laboratory of the Science and Technology Department of Jilin ProvinceYanjiP. R. China
| | - Tiefeng Jin
- Department of Pathology and Cancer Research CenterYanbian University Medical CollegeYanjiP. R. China
- Key Laboratory of the Science and Technology Department of Jilin ProvinceYanjiP. R. China
| | - Meihua Zhang
- Department of Ultrasound MedicineAffiliated Hospital of Yanbian UniversityYanjiP. R. China
- Department of Pathology and Cancer Research CenterYanbian University Medical CollegeYanjiP. R. China
- Key Laboratory of the Science and Technology Department of Jilin ProvinceYanjiP. R. China
| |
Collapse
|
|
10
|
Fakhri S, Moradi SZ, Abbaszadeh F, Faraji F, Amirian R, Sinha D, McMahon EG, Bishayee A. Targeting the key players of phenotypic plasticity in cancer cells by phytochemicals. Cancer Metastasis Rev 2024; 43:261-292. [PMID: 38169011 DOI: 10.1007/s10555-023-10161-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Accepted: 12/08/2023] [Indexed: 01/05/2024]
Abstract
Plasticity of phenotypic traits refers to an organism's ability to change in response to environmental stimuli. As a result, the response may alter an organism's physiological state, morphology, behavior, and phenotype. Phenotypic plasticity in cancer cells describes the considerable ability of cancer cells to transform phenotypes through non-genetic molecular signaling activities that promote therapy evasion and tumor metastasis via amplifying cancer heterogeneity. As a result of metastable phenotypic state transitions, cancer cells can tolerate chemotherapy or develop transient adaptive resistance. Therefore, new findings have paved the road in identifying factors and agents that inhibit or suppress phenotypic plasticity. It has also investigated novel multitargeted agents that may promise new effective strategies in cancer treatment. Despite the efficiency of conventional chemotherapeutic agents, drug toxicity, development of resistance, and high-cost limit their use in cancer therapy. Recent research has shown that small molecules derived from natural sources are capable of suppressing cancer by focusing on the plasticity of phenotypic responses. This systematic, comprehensive, and critical review analyzes the current state of knowledge regarding the ability of phytocompounds to target phenotypic plasticity at both preclinical and clinical levels. Current challenges/pitfalls, limitations, and future perspectives are also discussed.
Collapse
Affiliation(s)
- Sajad Fakhri
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran
| | - Seyed Zachariah Moradi
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran
| | - Fatemeh Abbaszadeh
- Department of Neuroscience, Faculty of Advanced Technologies in Medical Sciences, Iran University of Medical Sciences, Tehran, Iran
- Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farahnaz Faraji
- Department of Pharmaceutics, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, 6517838678, Iran
| | - Roshanak Amirian
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran
| | - Dona Sinha
- Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, Kolkata, 700 026, West Bengal, India
| | - Emily G McMahon
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL, 34211, USA
| | - Anupam Bishayee
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL, 34211, USA.
| |
Collapse
|
|
11
|
Singh S. Review on Natural Agents as Aromatase Inhibitors: Management of Breast Cancer. Comb Chem High Throughput Screen 2024; 27:2623-2638. [PMID: 37861041 DOI: 10.2174/0113862073269599231009115338] [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: 06/28/2023] [Revised: 08/16/2023] [Accepted: 09/21/2023] [Indexed: 10/21/2023]
Abstract
Breast cancer is a prevalent type of cancer that is typically hormone-dependent, caused by estrogen. Aromatase inhibitors are frequently utilised in the treatment of hormonereceptor- positive breast cancer because they prevent the enzyme aromatase from converting androgens to estrogens. Natural medicines with aromatase inhibitory characteristics have attracted interest as potential alternatives or complementary therapy to manufactured medications. This review discusses the function of natural agents as aromatase inhibitors in treating breast cancer. A variety of natural compounds have been investigated for their capacity to inhibit aromatase activity and lower estrogen levels. These agents include resveratrol from red wine and grapes, curcumin from turmeric extract and green teahigh in catechins, and other flavonoids such as genistein, luteolin and quercetin. It has been demonstrated that by decreasing estrogen synthesis, they can slow the growth of breast cancer cells that are dependent on estrogen. However, the clinical evidence supporting their efficacy and safety in breast cancer treatment is inadequate. More research is required to investigate the therapeutic potential of natural medicines, such as aromatase inhibitors, in treating breast cancer. The clinical trials are required to assess their efficacy, appropriate doses, and potential interactions with other therapies. In conclusion, natural aromatase inhibitory drugs are promising adjuncts in the treatment of hormone receptor-positive breast cancer. Their clinical value and safety profile, however, require additional investigation.
Collapse
Affiliation(s)
- Sonia Singh
- Institute of Pharmaceutical Research, GLA University Mathura, U.P: 281406, India
| |
Collapse
|
|
12
|
Paul T, Palaniyandi K, Gnanasampanthapandian D. Therapeutic Approaches to Increase the Survival Rate of Cancer Patients in the Younger and Older Population. Curr Aging Sci 2024; 17:16-30. [PMID: 38062658 DOI: 10.2174/0118746098241507231127114248] [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: 01/25/2023] [Revised: 06/25/2023] [Accepted: 09/22/2023] [Indexed: 05/18/2024]
Abstract
Various developments have been observed in the treatment of cancer patients, such as higher survival rates and better treatment outcomes. However, expecting similar outcomes in older patients remains a challenge. The main reason for this conclusion is the exclusion of older people from clinical trials for cancer drugs, as well as other factors, such as comorbidity, side effects, age-related frailties and their willingness to undergo multiple treatments. However, the discovery of new techniques and drug combinations has led to a significant improvement in the survival of the elderly population after the onset of the disease. On the other hand, cancer treatments have not become more complex for the younger population when compared to the older population, as the younger population tends to respond well to treatment trials and their physiological conditions are stable in response to treatments. In summary, this review correlates recent cancer treatment strategies and the corresponding responses and survival outcomes of older and younger patients.
Collapse
Affiliation(s)
- Tharrun Paul
- Cancer Science Laboratory, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, 603203, Chengalpattu, India
| | - Kanagaraj Palaniyandi
- Cancer Science Laboratory, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, 603203, Chengalpattu, India
| | - Dhanavathy Gnanasampanthapandian
- Cancer Science Laboratory, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, 603203, Chengalpattu, India
| |
Collapse
|
|
13
|
Vaz LD, Lainetti PDF, Leis AF, Pedro G, Fonseca-Alves CE, Laufer-Amorim R. Resveratrol and Viscum album anticancer effect in canine mammary tumor cell lines. BRAZILIAN JOURNAL OF VETERINARY PATHOLOGY 2024; 17:93-98. [DOI: 10.24070/bjvp.1983-0246.v17i2p93-98] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/02/2025]
Abstract
Mammary gland tumors are the most common neoplasms in female intact dogs and share some biological and histopathological aspects with those in women with breast cancer, making them a good model in comparative oncology. Resveratrol is a polyphenol found in several plants, and some studies have indicated that it acts in the neoplastic process as an anticancer drug. Viscum album is a hemiparasitic plant widely used as an adjuvant treatment for cancer in some countries. Thus, this study aimed to evaluate the antitumor potential of resveratrol and homeopathic Viscum album together and separately using two previously characterized canine mammary tumor cell lines (UNESP-CM9 and UNESP-CM60). The cell viability test (MTT) was performed, which revealed an IC50 of 3.11 μl/100 ml for UNESP-CM9 and 2.993 μl/100 ml for UNESP-CM60 for Viscum album, and for resveratrol, the IC50 was 281.6 μM for UNESP-CM9 and 105.5 μM for UNESP-CM60. The combination of both natural compounds led to tumor cell death at a lower IC50. The cell migration assay demonstrated an increase in cell migration time with both treatments. UNESP-CM9 closed 35.66% of the wounds in the control group and 15.51% of the wounds in the viscum group, while UNESP-CM60 closed 39.46% of the wounds in the control group and 19.95% of the wounds in the viscum group and 2.41% of the wounds in the resveratrol group. Thus, these two compounds have antitumor potential, making them possible alternatives to conventional treatments.
Collapse
|
|
14
|
Huang CY, Chen SH, Lin T, Liao YW, Chang YC, Chen CC, Yu CC, Chen CJ. Resveratrol attenuates advanced glycation end product-induced senescence and inflammation in human gingival fibroblasts. J Dent Sci 2024; 19:580-586. [PMID: 38303784 PMCID: PMC10829724 DOI: 10.1016/j.jds.2023.10.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Revised: 10/13/2023] [Indexed: 02/03/2024] Open
Abstract
Background/purpose The accumulation of advanced glycation end products (AGEs) lead to a series of immune responses such as: increased oxidative stress and inflammation which contribute to the development of diabetic complications and periodontal disease. Resveratrol is a natural compound that has anti-oxidant and anti-inflammatory effects. Studies have found that diabetes-induced periodontitis is mainly caused by oxidative stress, aging and increased inflammation. In view of resveratrol has been proposed to have the ability in anti-oxidant and anti-inflammation in a variety of tissues. However, the role of resveratrol in diabetic periodontitis remains to be investigated. In this study, we aimed to investigate the role of resveratrol in preventing and treating diabetic periodontitis. Materials and methods First, cell proliferation was measured in AGEs-treated human gingival fibroblast with or without resveratrol. We examined the reactive oxygen species (ROS) generation, senescence-associated beta-galactosidase (SA-β-gal) and senescence marker p16 in human gingival fibroblasts (HGFs) stimulated with AGEs with or without the treatment of resveratrol. To determine whether resveratrol has the potential to regulate inflammaging which is mediated via the NF-κB signaling pathway and, the expression of p65 and p-IκB were also investigated. Furthermore, the concentration of interleukin (IL)-6 and IL-8 were also measured in AGEs-stimulated HGFs treated with or without resveratrol. Results ROS generation, cell senescence, and the secretion of IL-6 and IL-8 were significantly upregulated following the treatment of AGEs. However, the administration of resveratrol suppresses the generation of IL-6 and IL-8 and cell senescence via inhibiting NF-κB signaling pathway. Our results revealed that resveratrol inhibits inflammaging by downregulating NF-κB signaling pathway. Conclusion According to our findings, AGEs increase senescence and the production of proinflammatory cytokines in the gingiva, while the administration of resveratrol impedes inflammaging via suppressing NF-κB signaling pathway.
Collapse
Affiliation(s)
- Chao-Yen Huang
- Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan
- Department of Emergency Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Szu-Han Chen
- Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan
- School of Dentistry, Chung Shan Medical University, Taichung, Taiwan
| | - Taichen Lin
- School of Dentistry, Chung Shan Medical University, Taichung, Taiwan
- Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Yi-Wen Liao
- Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan
- Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Yu-Cheng Chang
- Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Chun-Cheng Chen
- School of Dentistry, Chung Shan Medical University, Taichung, Taiwan
- Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Cheng-Chia Yu
- Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan
- School of Dentistry, Chung Shan Medical University, Taichung, Taiwan
- Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Chun-Jung Chen
- Division of Periodontics, Department of Dentistry, Chi Mei Medical Center, Tainan, Taiwan
| |
Collapse
|
|
15
|
Liu X, Cui S, Li W, Xie H, Shi L. Elucidation of the anti-colon cancer mechanism of Phellinus baumii polyphenol by an integrative approach of network pharmacology and experimental verification. Int J Biol Macromol 2023; 253:127429. [PMID: 37838121 DOI: 10.1016/j.ijbiomac.2023.127429] [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: 08/13/2023] [Revised: 09/27/2023] [Accepted: 10/11/2023] [Indexed: 10/16/2023]
Abstract
Colon cancer, a prevalent malignant tumor affecting the digestive system, presents a substantial risk to human health due to its high occurrence and mortality rates. Phellinus baumii polyphenol (PBP), a natural product derived from traditional Chinese medicine, has gained widespread popularity due to its low toxicity and minimal side effects, compared to radiation and chemotherapy. This study used an integrated approach of network pharmacology and experimental verification to elucidate the anti-colon cancer effects of PBP and its potential mechanisms. In network pharmacology, the identification of relevant targets involved a comprehensive search across multiple databases using keywords such as "active components of PBP" and "colon cancer". Venn diagram analysis was subsequently performed to ascertain the shared targets. To identify the key active components and core targets, we constructed a network of "Disease-Drug-Pathways-Targets" and a protein-protein interaction (PPI) network among the targets using Cytoscape 3.9.1. Furthermore, molecular docking was carried out to predict the binding affinity and conformation between the main active compounds (davallialactone and citrinin) of PBP and the core targets (TP53, STAT3, CASP3, CTNNB1, PARP1, MYC). To validate our findings, in vitro experiments were conducted. We verified that PBP exerted an anti-colon cancer effect on human colon cancer HCT116 cells by significantly inhibiting cell proliferation, promoting apoptosis and arresting the cell cycle in S phase by using Cell Counting Kit-8 (CCK-8) and flow cytometry. Finally, we determined the key regulatory proteins related to apoptosis and the cell cycle by western blot analysis, and proposed the potential mechanism by which PBP exerts an anti-colon cancer effect by inducing the caspase-dependent mitochondrial-mediated intrinsic apoptotic pathway and arresting the cell cycle in S phase in HCT116 cells. These results suggest that PBP possesses substantial potential for the treatment of colon cancer and may serve as a viable alternative therapeutic strategy in colon cancer treatment.
Collapse
Affiliation(s)
- Xue Liu
- College of Animal Sciences, Zhejiang University, Hangzhou 310058, China
| | - Shiyao Cui
- College of Animal Sciences, Zhejiang University, Hangzhou 310058, China; College of Life Sciences, Westlake University, Hangzhou 310058, China
| | - Wenle Li
- College of Animal Sciences, Zhejiang University, Hangzhou 310058, China
| | - Hongqing Xie
- College of Animal Sciences, Zhejiang University, Hangzhou 310058, China
| | - Liangen Shi
- College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
| |
Collapse
|
|
16
|
Burcher JT, DeLiberto LK, Allen AM, Kilpatrick KL, Bishayee A. Bioactive phytocompounds for oral cancer prevention and treatment: A comprehensive and critical evaluation. Med Res Rev 2023; 43:2025-2085. [PMID: 37143373 DOI: 10.1002/med.21969] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2022] [Revised: 04/05/2023] [Accepted: 04/12/2023] [Indexed: 05/06/2023]
Abstract
The high incidence of oral cancer combined with excessive treatment cost underscores the need for novel oral cancer preventive and therapeutic options. The value of natural agents, including plant secondary metabolites (phytochemicals), in preventing carcinogenesis and representing expansive source of anticancer drugs have been established. While fragmentary research data are available on antioral cancer effects of phytochemicals, a comprehensive and critical evaluation of the potential of these agents for the prevention and intervention of human oral malignancies has not been conducted according to our knowledge. This study presents a complete and critical analysis of current preclinical and clinical results on the prevention and treatment of oral cancer using phytochemicals. Our in-depth analysis highlights anticancer effects of various phytochemicals, such as phenolics, terpenoids, alkaloids, and sulfur-containing compounds, against numerous oral cancer cells and/or in vivo oral cancer models by antiproliferative, proapoptotic, cell cycle-regulatory, antiinvasive, antiangiogenic, and antimetastatic effects. Bioactive phytochemicals exert their antineoplastic effects by modulating various signaling pathways, specifically involving the epidermal growth factor receptor, cytokine receptors, toll-like receptors, and tumor necrosis factor receptor and consequently alter the expression of downstream genes and proteins. Interestingly, phytochemicals demonstrate encouraging effects in clinical trials, such as reduction of oral lesion size, cell growth, pain score, and development of new lesions. While most phytochemicals displayed minimal toxicity, concerns with bioavailability may limit their clinical application. Future directions for research include more in-depth mechanistic in vivo studies, administration of phytochemicals using novel formulations, investigation of phytocompounds as adjuvants to conventional treatment, and randomized clinical trials.
Collapse
Affiliation(s)
- Jack T Burcher
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
| | - Lindsay K DeLiberto
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
| | - Andrea M Allen
- School of Dental Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
| | - Kaitlyn L Kilpatrick
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
| | - Anupam Bishayee
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, Florida, USA
| |
Collapse
|
|
17
|
da Silva FC, Brandão DC, Ferreira EA, Siqueira RP, Ferreira HSV, Da Silva Filho AA, Araújo TG. Tailoring Potential Natural Compounds for the Treatment of Luminal Breast Cancer. Pharmaceuticals (Basel) 2023; 16:1466. [PMID: 37895937 PMCID: PMC10610388 DOI: 10.3390/ph16101466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 09/24/2023] [Accepted: 09/29/2023] [Indexed: 10/29/2023] Open
Abstract
Breast cancer (BC) is the most diagnosed cancer worldwide, mainly affecting the epithelial cells from the mammary glands. When it expresses the estrogen receptor (ER), the tumor is called luminal BC, which is eligible for endocrine therapy with hormone signaling blockade. Hormone therapy is essential for the survival of patients, but therapeutic resistance has been shown to be worrying, significantly compromising the prognosis. In this context, the need to explore new compounds emerges, especially compounds of plant origin, since they are biologically active and particularly promising. Natural products are being continuously screened for treating cancer due to their chemical diversity, reduced toxicity, lower side effects, and low price. This review summarizes natural compounds for the treatment of luminal BC, emphasizing the activities of these compounds in ER-positive cells. Moreover, their potential as an alternative to endocrine resistance is explored, opening new opportunities for the design of optimized therapies.
Collapse
Affiliation(s)
- Fernanda Cardoso da Silva
- Laboratory of Genetics and Biotechnology, Institute of Biotechnology, Universidade Federal de Uberlândia, Patos de Minas 38700-002, MG, Brazil; (F.C.d.S.); (D.C.B.); (R.P.S.); (H.S.V.F.)
| | - Douglas Cardoso Brandão
- Laboratory of Genetics and Biotechnology, Institute of Biotechnology, Universidade Federal de Uberlândia, Patos de Minas 38700-002, MG, Brazil; (F.C.d.S.); (D.C.B.); (R.P.S.); (H.S.V.F.)
| | - Everton Allan Ferreira
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Juiz de Fora, Juiz de Fora 36036-900, MG, Brazil; (E.A.F.); (A.A.D.S.F.)
| | - Raoni Pais Siqueira
- Laboratory of Genetics and Biotechnology, Institute of Biotechnology, Universidade Federal de Uberlândia, Patos de Minas 38700-002, MG, Brazil; (F.C.d.S.); (D.C.B.); (R.P.S.); (H.S.V.F.)
| | - Helen Soares Valença Ferreira
- Laboratory of Genetics and Biotechnology, Institute of Biotechnology, Universidade Federal de Uberlândia, Patos de Minas 38700-002, MG, Brazil; (F.C.d.S.); (D.C.B.); (R.P.S.); (H.S.V.F.)
| | - Ademar Alves Da Silva Filho
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Juiz de Fora, Juiz de Fora 36036-900, MG, Brazil; (E.A.F.); (A.A.D.S.F.)
| | - Thaise Gonçalves Araújo
- Laboratory of Genetics and Biotechnology, Institute of Biotechnology, Universidade Federal de Uberlândia, Patos de Minas 38700-002, MG, Brazil; (F.C.d.S.); (D.C.B.); (R.P.S.); (H.S.V.F.)
- Laboratory of Nanobiotechnology Prof. Dr. Luiz Ricardo Goulart Filho, Institute of Biotechnology, Universidade Federal de Uberlândia, Uberlandia 38405-302, MG, Brazil
| |
Collapse
|
|
18
|
Shi S, Li J, Zhang Z, Tu H, Max C. Isorhapontigenin (ISO) inhibits malignant cell transformation, migration, and invasion through MEG3/NEDD9 signaling in Cr(VI)-transformed cells. Toxicol Appl Pharmacol 2023; 476:116661. [PMID: 37619952 PMCID: PMC10874125 DOI: 10.1016/j.taap.2023.116661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 08/15/2023] [Accepted: 08/18/2023] [Indexed: 08/26/2023]
Abstract
Cr(VI) compounds are confirmed human carcinogens. Maternally expression 3 (MEG3) is the first long non-coding RNA to be identified as a tumor suppressor. MEG3 is frequently downregulated or lost in various primary human tumor tissues and cancer cell lines. Downregulation of MEG3 is associated with cancer initiation, progression, and metastasis. Our previous study has revealed that MEG3 was lost and NEDD9 was upregulated in Cr(VI)-transformed cells compared to those in passage-matched normal BEAS-2B cells. Overexpression of MEG3 reduced NEDD9. β-Catenin was activated in Cr(VI)-transformed cells, overexpression of MEG3 or knockdown of NEDD9 inhibited the activation of β-Catenin. The results from the present study showed that isorhapontigenin (ISO) treatment is able to suppress cell proliferation, migration, and invasion of Cr(VI)-transformed cells. Further study showed that ISO treatment in Cr(VI)-transformed cells decreases the levels of Ki67, a biomarker for cell proliferation, and of cyclin D1, a regulator for the cell cycle. ISO elevated the MEG3 expression level in Cr(VI)-transformed cells. The DNA methylation transferases DNMT3a, DNMT3b, and DNMT1 levels were reduced upon ISO treatment. ISO treatment decreased both mRNA and protein levels of NEDD9. In addition, ISO treatment reduced the activation of β-catenin. Slug was upregulated and E-Cadherin was downregulated in Cr(VI)-transformed cells, treatment with ISO decreased Slug and increased E-Cadherin. This study demonstrated that ISO is a potent therapeutical agent against lung cancer induced by Cr(VI).
Collapse
Affiliation(s)
- Sophia Shi
- Department of Environmental Medicine, New York University Grossman School of Medicine, 341 East 25(th) Street, NY, New York 10010, United States of America
| | - Jingxia Li
- Department of Environmental Medicine, New York University Grossman School of Medicine, 341 East 25(th) Street, NY, New York 10010, United States of America
| | - Zhuo Zhang
- Department of Environmental Medicine, New York University Grossman School of Medicine, 341 East 25(th) Street, NY, New York 10010, United States of America
| | - Huailu Tu
- Department of Environmental Medicine, New York University Grossman School of Medicine, 341 East 25(th) Street, NY, New York 10010, United States of America
| | - Costa Max
- Department of Environmental Medicine, New York University Grossman School of Medicine, 341 East 25(th) Street, NY, New York 10010, United States of America.
| |
Collapse
|
|
19
|
Sun DP, Chen JT, Yang ST, Chen TH, Liu SH, Chen RM. Resveratrol triggers the ER stress-mediated intrinsic apoptosis of neuroblastoma cells coupled with suppression of Rho-dependent migration and consequently prolongs mouse survival. Chem Biol Interact 2023; 382:110645. [PMID: 37482209 DOI: 10.1016/j.cbi.2023.110645] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 07/15/2023] [Accepted: 07/21/2023] [Indexed: 07/25/2023]
Abstract
Neuroblastoma, the most common childhood tumor, are highly malignant and fatal because neuroblastoma cells extremely defend against apoptotic targeting. Traditional treatments for neuroblastomas are usually ineffective and lead to serious side effects and poor prognoses. In this study, we investigated the molecular mechanisms of resveratrol-induced insults to neuroblastoma cells and survival extension of nude mice with neuroblastomas, especially in the endoplasmic reticular (ER) stress-intracellular reactive oxygen species (iROS) axis-mediated signals. Resveratrol specifically killed neuroblastoma cells mainly via apoptosis and autophagy rather than necrosis. As to the mechanisms, resveratrol time-dependently triggered productions of Grp78 protein and iROS in neuroblastoma cells. Attenuating the ER stress-iROS signaling axis significantly suppressed resveratrol-induced autophagy, DNA damage, and cell apoptosis. Successively, resveratrol decreased phosphorylation of retinoblastoma protein and induced cell cycle arrest at the S phase, translocation of Bak protein to mitochondria, a reduction in the mitochondrial membrane potential, cascade activation of caspases-9, -3, and -6, and DNA fragmentation. Moreover, weakening the ER stress-iROS axis concomitantly overcome resveratrol-induced decreases in translocation of Rho protein to membranes and succeeding cell migration. Interestingly, administration of resveratrol did not cause significant side effects but could protect the neuroblastoma-bearing nude mice from body weight loss and consequently extended the animal survival. In parallel, resveratrol elevated levels of Grp78 and then induced cell apoptosis in neuroblastoma tissues. This study has shown that resveratrol could kill neuroblastoma cells and extend survival of animals with neuroblastomas by triggering the ER stress-iROS-involved intrinsic apoptosis and suppression of Rho-dependent cell migration. Our results imply the potential of resveratrol as a drug candidate for chemotherapy of neuroblastoma patients.
Collapse
Affiliation(s)
- Ding-Ping Sun
- Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan; Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Jui-Tai Chen
- Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Shun-Tai Yang
- Division of Nephrology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Tso-Hsiao Chen
- Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Shing-Hwa Liu
- Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, 100, Taiwan
| | - Ruei-Ming Chen
- Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan; Anesthesiology and Health Policy Research Center, Taipei Medical University Hospital, Taipei, Taiwan; International Ph.D. Program for Cell Therapy and Regeneration Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan.
| |
Collapse
|
|
20
|
Choudhary N, Bawari S, Burcher JT, Sinha D, Tewari D, Bishayee A. Targeting Cell Signaling Pathways in Lung Cancer by Bioactive Phytocompounds. Cancers (Basel) 2023; 15:3980. [PMID: 37568796 PMCID: PMC10417502 DOI: 10.3390/cancers15153980] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 07/29/2023] [Accepted: 07/31/2023] [Indexed: 08/13/2023] Open
Abstract
Lung cancer is a heterogeneous group of malignancies with high incidence worldwide. It is the most frequently occurring cancer in men and the second most common in women. Due to its frequent diagnosis and variable response to treatment, lung cancer was reported as the top cause of cancer-related deaths worldwide in 2020. Many aberrant signaling cascades are implicated in the pathogenesis of lung cancer, including those involved in apoptosis (B cell lymphoma protein, Bcl-2-associated X protein, first apoptosis signal ligand), growth inhibition (tumor suppressor protein or gene and serine/threonine kinase 11), and growth promotion (epidermal growth factor receptor/proto-oncogenes/phosphatidylinositol-3 kinase). Accordingly, these pathways and their signaling molecules have become promising targets for chemopreventive and chemotherapeutic agents. Recent research provides compelling evidence for the use of plant-based compounds, known collectively as phytochemicals, as anticancer agents. This review discusses major contributing signaling pathways involved in the pathophysiology of lung cancer, as well as currently available treatments and prospective drug candidates. The anticancer potential of naturally occurring bioactive compounds in the context of lung cancer is also discussed, with critical analysis of their mechanistic actions presented by preclinical and clinical studies.
Collapse
Affiliation(s)
- Neeraj Choudhary
- Department of Pharmacognosy, GNA School of Pharmacy, GNA University, Phagwara 144 401, India
| | - Sweta Bawari
- Amity Institute of Pharmacy, Amity University, Noida 201 301, India
| | - Jack T. Burcher
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA
| | - Dona Sinha
- Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, Kolkata 700 026, India
| | - Devesh Tewari
- Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, New Delhi 110 017, India
| | - Anupam Bishayee
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA
| |
Collapse
|
|
21
|
Croley CR, Pumarol J, Delgadillo BE, Cook AC, Day F, Kaceli T, Ward CC, Husain I, Husain A, Banerjee S, Bishayee A. Signaling pathways driving ocular malignancies and their targeting by bioactive phytochemicals. Pharmacol Ther 2023:108479. [PMID: 37330112 DOI: 10.1016/j.pharmthera.2023.108479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Revised: 06/05/2023] [Accepted: 06/12/2023] [Indexed: 06/19/2023]
Abstract
Ocular cancers represent a rare pathology. The American Cancer Society estimates that 3,360 cases of ocular cancer occur annually in the United States. The major types of cancers of the eye include ocular melanoma (also known as uveal melanoma), ocular lymphoma, retinoblastoma, and squamous cell carcinoma. While uveal melanoma is one of the primary intraocular cancers with the highest occurrence in adults, retinoblastoma remains the most common primary intraocular cancer in children, and squamous cell carcinoma presents as the most common conjunctival cancer. The pathophysiology of these diseases involves specific cell signaling pathways. Oncogene mutations, tumor suppressor mutations, chromosome deletions/translocations and altered proteins are all described as causal events in developing ocular cancer. Without proper identification and treatment of these cancers, vision loss, cancer spread, and even death can occur. The current treatments for these cancers involve enucleation, radiation, excision, laser treatment, cryotherapy, immunotherapy, and chemotherapy. These treatments present a significant burden to the patient that includes a possible loss of vision and a myriad of side effects. Therefore, alternatives to traditional therapy are urgently needed. Intercepting the signaling pathways for these cancers with the use of naturally occurring phytochemicals could be a way to relieve both cancer burden and perhaps even prevent cancer occurrence. This research aims to present a comprehensive review of the signaling pathways involved in various ocular cancers, discuss current therapeutic options, and examine the potential of bioactive phytocompounds in the prevention and targeted treatment of ocular neoplasms. The current limitations, challenges, pitfalls, and future research directions are also discussed.
Collapse
Affiliation(s)
- Courtney R Croley
- Healthcare Corporation of America, Department of Ophthalmology, Morsani College of Medicine, University of South Florida, Hudson, FL 34667, USA
| | - Joshua Pumarol
- Ross University School of Medicine, Miramar, FL 33027, USA
| | - Blake E Delgadillo
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA
| | - Andrew C Cook
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA
| | - Faith Day
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA
| | - Tea Kaceli
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA
| | - Caroline C Ward
- Morsani College of Medicine, University of South Florida, Tampa, FL 33602, USA
| | - Imran Husain
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Erie, PA 16509, USA
| | - Ali Husain
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Erie, PA 16509, USA
| | - Sabyasachi Banerjee
- Department of Pharmaceutical Chemistry, Gupta College of Technological Sciences, Asansol 713 301, India
| | - Anupam Bishayee
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA.
| |
Collapse
|
|
22
|
Wani MY, Ganie NA, Wani DM, Wani AW, Dar SQ, Khan AH, A Khan N, Manzar MS, Dehghani MH. The phenolic components extracted from mulberry fruits as bioactive compounds against cancer: A review. Phytother Res 2023; 37:1136-1152. [PMID: 36592613 DOI: 10.1002/ptr.7713] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 11/02/2022] [Accepted: 11/26/2022] [Indexed: 01/03/2023]
Abstract
In Asia, mulberry has long been used to treat various infectious and internal ailments as a traditional medication. The compounds found in it have the potential to improve human health. Because there is no approved and defined evaluation procedure, it has not been formally or scientifically recognized. As a result of these investigations, a new frontier in traditional Chinese medicine has opened up, with the possibility of modernization, for the interaction between active components of mulberry and their biological activities. These studies have used current biotechnological technologies. For ages, mulberry has been used as an herbal remedy in Asia to cure various diseases and internal disorders. It has a high concentration of bioactive chemicals that benefit human health. The most abundant phenolic components extracted from white mulberry leaves are flavonoids (Kuwanons, Moracinflavans, Moragrols, and Morkotins), phenolic acids, alkaloids, and so forth. Flavonoids, benzofurans, chalcones, and alkaloids have been discovered to have cytotoxic effects on human cancer cell lines. There is growing evidence that mulberry fruits can potentially prevent cancer and other aging-related disorders due to their high concentration of bioactive polyphenolic-rich compounds and macro and micronutrients. Anthocyanins are rapidly absorbed after eating, arriving in the plasmalemma within 15-50 min and entirely removed after 6-8 hr. Due to a lack of an approved and consistent technique for its examination, it has yet to be formally or scientifically recognized. The mulberry plant is commercially grown for silkworm rearing, and less attention is paid to its bioactive molecules, which have a lot of applications in human health. This review paper discusses the phenolic compounds of white mulberry and black mulberry in detail concerning their role in cancer prevention.
Collapse
Affiliation(s)
- Mohd Younus Wani
- College of Temperate Sericulture, Mirgund, SKUAST-Kashmir, Shalimar, India
| | - N A Ganie
- College of Temperate Sericulture, Mirgund, SKUAST-Kashmir, Shalimar, India
| | - D M Wani
- Division of Entomology, SKUAST-Kashmir, Shalimar, India
| | - Ab Waheed Wani
- Division of Fruit Science, SKUAST-Kashmir, Shalimar, India
| | - S Q Dar
- Division of Fruit Science, SKUAST-Kashmir, Shalimar, India
| | - Afzal Husain Khan
- Civil Engineering Department, College of Engineering, Jazan University, Jizan, Saudi Arabia
| | - Nadeem A Khan
- Civil Engineering Department, Mewat Engineering College, New Delhi, India
| | - Mohammad Saood Manzar
- Department of Environmental Engineering, College of Engineering, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Mohammad Hadi Dehghani
- Department of Environmental Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.,Institute for Environmental Research, Center for Solid Waste Research, Tehran University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
23
|
Xia C, Wang G, Chen L, Geng H, Yao J, Bai Z, Deng L. Trans-gnetin H isolated from the seeds of Paeonia species induces autophagy via inhibiting mTORC1 signalling through AMPK activation. Cell Prolif 2023; 56:e13360. [PMID: 36377675 PMCID: PMC9977667 DOI: 10.1111/cpr.13360] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Revised: 10/28/2022] [Accepted: 11/02/2022] [Indexed: 11/16/2022] Open
Abstract
Paeonia is a well-known species of ornamental plants, traditional Chinese medicines, and emerging oilseed crops. Apart from nutritional unsaturated fatty acids, the seeds of peonies are rich in stilbenes characterized by their wide-ranging health-promoting properties. Although the typical stilbene resveratrol has been widely reported for its multiple bioactivities, it remains uncertain whether the trimer of resveratrol trans-gnetin H has properties that regulate cancer cell viability, let alone the underlying mechanism. Autophagy regulated by trans-gnetin H was detected by western blotting, immunofluorescence, and quantitative real-time PCR. The effects of trans-gnetin H on apoptosis and proliferation were examined by flow cytometry, colony formation and Cell Counting Kit-8 assays. Trans-gnetin H significantly inhibits cancer cell viability through autophagy by suppressing the phosphorylation of TFEB and promoting its nuclear transport. Mechanistically, trans-gnetin H inhibits the activation and lysosome translocation of mTORC1 by inhibiting the activation of AMPK, indicating that AMPK is a checkpoint for mTORC1 inactivation induced by trans-gnetin H. Moreover, the binding of TSC2 to Rheb was markedly increased in response to trans-gnetin H stimulation. Similarly, trans-gnetin H inhibited the interaction between Raptor and RagC in an AMPK-dependent manner. More importantly, trans-gnetin H-mediated autophagy highly depends on the AMPK-mTORC1 axis. We propose a regulatory mechanism by which trans-gnetin H inhibits the activation of the mTORC1 pathway to control cell autophagy.
Collapse
Affiliation(s)
- Chao Xia
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
| | - Guoyan Wang
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
| | - Lei Chen
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
| | - Huijun Geng
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
| | - Junhu Yao
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
| | - Zhangzhen Bai
- College of Landscape Architecture and Arts, Northwest A&F University, Yangling, Shaanxi, China
| | - Lu Deng
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
| |
Collapse
|
|
24
|
Harries LW. Dysregulated RNA processing and metabolism: a new hallmark of ageing and provocation for cellular senescence. FEBS J 2023; 290:1221-1234. [PMID: 35460337 DOI: 10.1111/febs.16462] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 03/28/2022] [Accepted: 04/21/2022] [Indexed: 12/23/2022]
Abstract
The human genome is capable of producing hundreds of thousands of different proteins and non-coding RNAs from <20 000 genes, in a co-ordinated and regulated fashion. This is achieved by a collection of phenomena known as mRNA processing and metabolism, and encompasses events in the life cycle of an RNA from synthesis to degradation. These factors are critical determinants of cellular adaptability and plasticity, which allows the cell to adjust its transcriptomic output in response to its internal and external environment. Evidence is building that dysfunctional RNA processing and metabolism may be a key contributor to the development of cellular senescence. Senescent cells by definition have exited cell cycle, but have gained functional features such as the secretion of the senescence-associated secretory phenotype (SASP), a known driver of chronic disease and perhaps even ageing itself. In this review, I will outline the impact of dysregulated mRNA processing and metabolism on senescence and ageing at the level of genes, cells and systems, and describe the mechanisms by which progressive deterioration in these processes may impact senescence and organismal ageing. Finally, I will present the evidence implicating this important process as a new hallmark of ageing, which could be harnessed in the future to develop new senotherapeutic interventions for chronic disease.
Collapse
|
|
25
|
De S, Paul S, Manna A, Majumder C, Pal K, Casarcia N, Mondal A, Banerjee S, Nelson VK, Ghosh S, Hazra J, Bhattacharjee A, Mandal SC, Pal M, Bishayee A. Phenolic Phytochemicals for Prevention and Treatment of Colorectal Cancer: A Critical Evaluation of In Vivo Studies. Cancers (Basel) 2023; 15:993. [PMID: 36765950 PMCID: PMC9913554 DOI: 10.3390/cancers15030993] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 01/30/2023] [Accepted: 01/30/2023] [Indexed: 02/08/2023] Open
Abstract
Colorectal cancer (CRC) is the third most diagnosed and second leading cause of cancer-related death worldwide. Limitations with existing treatment regimens have demanded the search for better treatment options. Different phytochemicals with promising anti-CRC activities have been reported, with the molecular mechanism of actions still emerging. This review aims to summarize recent progress on the study of natural phenolic compounds in ameliorating CRC using in vivo models. This review followed the guidelines of the Preferred Reporting Items for Systematic Reporting and Meta-Analysis. Information on the relevant topic was gathered by searching the PubMed, Scopus, ScienceDirect, and Web of Science databases using keywords, such as "colorectal cancer" AND "phenolic compounds", "colorectal cancer" AND "polyphenol", "colorectal cancer" AND "phenolic acids", "colorectal cancer" AND "flavonoids", "colorectal cancer" AND "stilbene", and "colorectal cancer" AND "lignan" from the reputed peer-reviewed journals published over the last 20 years. Publications that incorporated in vivo experimental designs and produced statistically significant results were considered for this review. Many of these polyphenols demonstrate anti-CRC activities by inhibiting key cellular factors. This inhibition has been demonstrated by antiapoptotic effects, antiproliferative effects, or by upregulating factors responsible for cell cycle arrest or cell death in various in vivo CRC models. Numerous studies from independent laboratories have highlighted different plant phenolic compounds for their anti-CRC activities. While promising anti-CRC activity in many of these agents has created interest in this area, in-depth mechanistic and well-designed clinical studies are needed to support the therapeutic use of these compounds for the prevention and treatment of CRC.
Collapse
Affiliation(s)
- Samhita De
- Division of Molecular Medicine, Bose Institute, Kolkata 700 054, India
| | - Sourav Paul
- Department of Biotechnology, National Institute of Technology, Durgapur 713 209, India
| | - Anirban Manna
- Division of Molecular Medicine, Bose Institute, Kolkata 700 054, India
| | | | - Koustav Pal
- Jawaharlal Institute Post Graduate Medical Education and Research, Puducherry 605 006, India
| | - Nicolette Casarcia
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA
| | - Arijit Mondal
- Department of Pharmaceutical Chemistry, M.R. College of Pharmaceutical Sciences and Research, Balisha 743 234, India
| | - Sabyasachi Banerjee
- Department of Pharmaceutical Chemistry, Gupta College of Technological Sciences, Asansol 713 301, India
| | - Vinod Kumar Nelson
- Department of Pharmacology, Raghavendra Institute of Pharmaceutical Education and Research, Anantapur 515 721, India
| | - Suvranil Ghosh
- Division of Molecular Medicine, Bose Institute, Kolkata 700 054, India
| | - Joyita Hazra
- Department of Biotechnology, Indian Institute of Technology, Chennai 600 036, India
| | - Ashish Bhattacharjee
- Department of Biotechnology, National Institute of Technology, Durgapur 713 209, India
| | | | - Mahadeb Pal
- Division of Molecular Medicine, Bose Institute, Kolkata 700 054, India
| | - Anupam Bishayee
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA
| |
Collapse
|
|
26
|
Mahmoud AF, Aboumanei MH, Abd-Allah WH, Swidan MM, Sakr TM. New frontier radioiodinated probe based on in silico resveratrol repositioning for microtubules dynamic targeting. Int J Radiat Biol 2023; 99:281-291. [PMID: 35549606 DOI: 10.1080/09553002.2022.2078001] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
PURPOSE As the 'de novo' drug discovery faces a highly attrition rates, drug repositioning procures a heighten concern in identifying novel uses for existing medications. This study aimed to fabricate radioiodinated resveratrol as a potent microtubules interfering agent for cancer theragnosis. METHODS Resveratrol was radiolabeled with radioactive iodine where the radioiodination efficiency was enlightened and the computational approaches were employed to investigate the affinity and specificity with tubulins. Furthermore, the in-vivo distribution and pharmacokinetic studies in normal and tumor induced mice were investigated. RESULTS The maximum radioiodination yield (94.6 ± 1.66) was achieved at optimum preparation parameters stated as 100 μg/mL of oxidizing agent, 100 μg/ml of resveratrol, reaction time of 30 min and reaction pH 5. The in silico studies showed that di-iodinated resveratrol (compound 6) exhibited the best binding score (-34.46) and interaction with the β-tubulin binding site. The in vivo distribution in tumor models revealed a significant accumulation (4.02% ID/g) in tumor lesion at 60 min p.i. The rate of drug elimination demonstrated a mono-exponential decline of radioactivity versus time in the blood. CONCLUSION Radioiodinated resveratrol revealed good microtubules targeting which render it as a novel theranostic probe for cancer management.
Collapse
Affiliation(s)
- Ashgan F Mahmoud
- Labeled Compounds Department, Hot Labs Center, Egyptian Atomic Energy Authority, Cairo, Egypt
| | - Mohamed H Aboumanei
- Labeled Compounds Department, Hot Labs Center, Egyptian Atomic Energy Authority, Cairo, Egypt
| | - Walaa Hamada Abd-Allah
- Pharmaceutical Chemistry Department, College of Pharmaceutical Science and Drug Manufacturing, Misr University for Science and Technology, Giza, Egypt
| | - Mohamed M Swidan
- Labeled Compounds Department, Hot Labs Center, Egyptian Atomic Energy Authority, Cairo, Egypt.,Radioisotopes Production Facility, Second Egyptian Research Reactor Complex, Egyptian Atomic Energy Authority, Cairo, Egypt
| | - Tamer M Sakr
- Radioisotopes Production Facility, Second Egyptian Research Reactor Complex, Egyptian Atomic Energy Authority, Cairo, Egypt.,Radioactive Isotopes and Generator Department, Hot Labs Center, Egyptian Atomic Energy Authority, Cairo, Egypt
| |
Collapse
|
|
27
|
Resveratrol derivatives: Synthesis and their biological activities. Eur J Med Chem 2023; 246:114962. [PMID: 36463729 DOI: 10.1016/j.ejmech.2022.114962] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 11/11/2022] [Accepted: 11/23/2022] [Indexed: 11/27/2022]
Abstract
Resveratrol, a natural compound known especially for its antioxidant properties and protective action, opens the door for both it and its structural derivatives to be considered not only as chemopreventive but also as cancer chemotherapeutic agents. Due to the pharmacokinetic problems of resveratrol that demonstrate its poor bioavailability, the study of new derivatives is of interest. Thus, in this work (E)-stilbenes derived directly from resveratrol and other cyclic analogues containing the benzofuran or indole nucleus have been synthesized. The synthesized compounds have been evaluated for their ability to affect tumor growth in vitro. Compounds 2, 3, 4 and 5 have shown cytotoxicity in human colon cancer (HT-29) and human pancreatic adenocarcinoma cells (MIA PaCa-2) higher than those of (E)-resveratrol. The indolic derivative 13, a cyclic analog of resveratrol, has shown in vitro cytotoxic activity 8 times higher than resveratrol against HT-29 cancer cells. The cyclic derivatives 8, 9 and 12 showed a high inhibition of cell growth in HCT-116 (KRas mutant) at 20 μM, while 13 shows moderate antiangiogenesis activity at 10 μM.
Collapse
|
|
28
|
Sung WJ, Hong J. Targeting lncRNAs of colorectal cancers with natural products. Front Pharmacol 2023; 13:1050032. [PMID: 36699052 PMCID: PMC9868597 DOI: 10.3389/fphar.2022.1050032] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Accepted: 12/22/2022] [Indexed: 01/11/2023] Open
Abstract
Non-coding RNA (ncRNA) is one of the functional classes of RNA that has a regulatory role in various cellular processes, such as modulation of disease onset, progression, and prognosis. ncRNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have been actively studied in recent years. The change in ncRNA levels is being actively studied in numerous human diseases, especially auto-immune disorders and cancers; however, targeting and regulating ncRNA with natural products to cure cancer has not been fully established. Recently many groups reported the relationship between ncRNA and natural products showing promising effects to serve as additional therapeutic approaches to cure cancers. This mini-review summarizes the aspects of lncRNAs related to cancer biology focusing on colorectal cancers that natural products can target.
Collapse
Affiliation(s)
- Woo Jung Sung
- Department of Pathology, Daegu Catholic University School of Medicine, Daegu, South Korea
| | - Jaewoo Hong
- Department of Physiology, Daegu Catholic University School of Medicine, Daegu, South Korea,*Correspondence: Jaewoo Hong,
| |
Collapse
|
|
29
|
El-Sheikh MM, Abdel-Naby DH, El-Hazek RM, El-Ghazaly MA. Regulation of radiation-induced liver damage by modulation of SIRT-1 activity: In vivo rat model. Cell Biochem Funct 2023; 41:67-77. [PMID: 36259113 DOI: 10.1002/cbf.3762] [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: 09/06/2022] [Revised: 10/06/2022] [Accepted: 10/10/2022] [Indexed: 01/11/2023]
Abstract
Silent information regulator 1 (SIRT-1), a nicotinamide adenine dinucleotide-dependent deacetylase, was found to regulate cell apoptosis, inflammation, and oxidative stress response in living organisms. Therefore, the role of SIRT-1 in regulating forkhead box O/poly ADP-ribose polymerase-1 (FOXO-1/PARP-1) signaling could provide the necessary validation for developing new pharmacological targets for the promotion or inhibition of SIRT-1 activity toward radiation sensitivity. In the present study, the SIRT-1 signaling pathway is being investigated to study the possible modulatory effect of resveratrol (RSV, SIRT-1 activator) versus nicotinamide (NAM, SIRT-1 inhibitor) in case of liver damage induced by whole-body gamma irradiation. Rats were exposed to 6 Gy gamma radiation after being pretreated with either RSV (10 mg/kg/day) or NAM (100 mg/kg/day) for 5 days, and subsequent examining hepatic morphological changes and apoptotic markers were assessed. The expression of SIRT-1, FOXO-1, and cleaved PARP-1 in the liver was analyzed. RSV improved radiation-induced apoptosis, mitochondrial dysfunction, and inflammation signified by low expression of caspase-3, lactate dehydrogenase, complex-I activity, myeloperoxidase, and total nitric oxide content. RSV increased the expression of SIRT-1, whereas cleaved PARP-1 and FOXO-1 were suppressed. These protective effects were suppressed by inhibition of SIRT-1 activity using NAM. These findings suggest that RSV can attenuate radiation-induced hepatic injury by reducing apoptosis and inflammation via SIRT-1 activity modulation.
Collapse
Affiliation(s)
- Marwa M El-Sheikh
- Department of Drug Radiation Research, National Centre for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority, Nasr City, Cairo, Egypt
| | - Doaa H Abdel-Naby
- Department of Drug Radiation Research, National Centre for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority, Nasr City, Cairo, Egypt
| | - Rania M El-Hazek
- Department of Drug Radiation Research, National Centre for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority, Nasr City, Cairo, Egypt
| | - Mona A El-Ghazaly
- Department of Drug Radiation Research, National Centre for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority, Nasr City, Cairo, Egypt
| |
Collapse
|
|
30
|
Harwansh RK, Yadav P, Deshmukh R. Current Insight into Novel Delivery Approaches of Resveratrol for Improving Therapeutic Efficacy and Bioavailability with its Clinical Updates. Curr Pharm Des 2023; 29:2921-2939. [PMID: 38053352 DOI: 10.2174/0113816128282713231129094715] [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: 09/17/2023] [Revised: 10/22/2023] [Accepted: 11/02/2023] [Indexed: 12/07/2023]
Abstract
Resveratrol (RSV) is a polyphenolic phytoalexin, and belongs to the stilbene family. RSV has several therapeutic activities such as cardioprotective, anticancer, and antioxidant. Apart from its therapeutic benefits, its pharmacological uses are limited due to low solubility, poor bioavailability, and short biological halflife. A researcher continuously focuses on overcoming the limitations of RSV through nanotechnology platforms to get the optimum health benefits. In this context, nanocarriers are pioneering to overcome these drawbacks. Nanocarriers possess high drug loading capacity, thermal stability, low production cost, longer shelflife, etc. Fortunately, scientists were proficient in delivering resveratrol-based nanocarriers in the present scenario. Nanocarriers can deliver drugs to the target sites without compromising the bioavailability. Thus, this review highlights how the latest nanocarrier systems overcome the shortcomings of RSV, which will be good for improving therapeutic efficacy and bioavailability. Moreover, recent updates on resveratrol-based novel formulations and their clinical trials have been addressed to manage several health-related problems.
Collapse
Affiliation(s)
- Ranjit K Harwansh
- Institute of Pharmaceutical Research, GLA University, Mathura 281406, India
| | - Paras Yadav
- Institute of Pharmaceutical Research, GLA University, Mathura 281406, India
| | - Rohitas Deshmukh
- Institute of Pharmaceutical Research, GLA University, Mathura 281406, India
| |
Collapse
|
|
31
|
Mishra A, Pathak Y, Mishra SK, Prakash H, Tripathi V. Natural compounds as a potential modifier of stem cells renewal: Comparative analysis. Eur J Pharmacol 2022; 938:175412. [PMID: 36427534 DOI: 10.1016/j.ejphar.2022.175412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 11/09/2022] [Accepted: 11/21/2022] [Indexed: 11/25/2022]
Abstract
Cancer stem cells (CSCs) are indispensable for development, progression, drug resistance, and tumor metastasis. Current cancer-directed interventions target targeting rapidly dividing cancer cells and slow dividing CSCs, which are the root cause of cancer origin and recurrence. The most promising targets include several self-renewal pathways involved in the maintenance and renewal of CSCs, such as the Wnt/β-Catenin, Sonic Hedgehog, Notch, Hippo, Autophagy, and Ferroptosis. In view of safety, natural compounds are coming to the front line of treatment modalities for modifying various signaling pathways simultaneously involved in maintaining CSCs. Therefore, targeting CSCs with natural compounds is a promising approach to treating various types of cancers. In view of this, here we provide a comprehensive update on the current status of natural compounds that effectively tune key self-renewal pathways of CSCs. In addition, we highlighted surface expression markers in several types of cancer. We also emphasize how natural compounds target these self-renewal pathways to reduce therapy resistance and cancer recurrence properties of CSCs, hence providing valuable cancer therapeutic strategies. The inclusion of nutraceuticals is believed to enhance the therapeutic efficacy of current cancer-directed interventions significantly.
Collapse
Affiliation(s)
- Amaresh Mishra
- School of Biotechnology, Gautam Buddha University, Greater Noida, 201310, India
| | - Yamini Pathak
- School of Biotechnology, Gautam Buddha University, Greater Noida, 201310, India
| | | | - Hridayesh Prakash
- Amity Institute of Virology and Immunology, Amity University, Uttar Pradesh, India
| | - Vishwas Tripathi
- School of Biotechnology, Gautam Buddha University, Greater Noida, 201310, India.
| |
Collapse
|
|
32
|
Han DS, Lee HJ, Lee EO. Resveratrol suppresses serum-induced vasculogenic mimicry through impairing the EphA2/twist-VE-cadherin/AKT pathway in human prostate cancer PC-3 cells. Sci Rep 2022; 12:20125. [PMID: 36418859 PMCID: PMC9684476 DOI: 10.1038/s41598-022-24414-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 11/15/2022] [Indexed: 11/24/2022] Open
Abstract
Vasculogenic mimicry (VM) is closely related to cancer progression and metastasis, contributing to poor prognosis in patients with cancer. Resveratrol (RES) is well known to possess anti-cancer activity. This study explored the new role of RES in VM incidence in human prostate cancer (PCa) PC-3 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, transwell invasion, and three-dimensional culture VM tube formation assays were performed to check the cell viability, invasive ability, and vessel-like networks formation, respectively. VM-related proteins were detected by Western blots. The activity of metalloproteinase-2 (MMP-2) was identified by gelatin zymography. Vascular endothelial cadherin (VE-cadherin) mRNA was assessed by reverse transcriptase-polymerase chain reaction. Nuclear twist expression was observed by immunofluorescence assay. RES reduced serum-induced invasion and VM formation. Serum-induced phosphorylation of erythropoiethin-producing hepatoceullular A2 (EphA2) and the expression of VE-cadherin at the protein and mRNA levels were decreased after RES treatment. RES inhibited serum-induced expression and nuclear localization of twist. Serum-activated AKT signaling pathway, including MMP-2 and laminin subunit 5 gamma-2, was impaired by RES. These results suggested that RES may have an anti-VM effect through suppressing the EphA2/twist-VE-cadherin/AKT signaling cascade in PCa PC-3 cells.
Collapse
Affiliation(s)
- Deok-Soo Han
- grid.289247.20000 0001 2171 7818Department of Science in Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447 Republic of Korea
| | - Hyo-Jeong Lee
- grid.289247.20000 0001 2171 7818Department of Science in Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447 Republic of Korea ,grid.289247.20000 0001 2171 7818Department of Cancer Preventive Material Development, College of Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447 Republic of Korea
| | - Eun-Ok Lee
- grid.289247.20000 0001 2171 7818Department of Science in Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447 Republic of Korea ,grid.289247.20000 0001 2171 7818Department of Cancer Preventive Material Development, College of Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447 Republic of Korea
| |
Collapse
|
|
33
|
Effects of Natural Polyphenols on Skin and Hair Health: A Review. Molecules 2022; 27:molecules27227832. [PMID: 36431932 PMCID: PMC9695112 DOI: 10.3390/molecules27227832] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 11/10/2022] [Accepted: 11/11/2022] [Indexed: 11/15/2022] Open
Abstract
The skin is the largest organ of the body and plays multiple essential roles, ranging from regulating temperature, preventing infections, to ultimately affecting human health. A hair follicle is a complex cutaneous appendage. Skin diseases and hair loss have a significant effect on the quality of life and psychosocial adjustment of individuals. However, the available traditional drugs for treating skin and hair diseases may have some insufficiencies; therefore, a growing number of researchers are interested in natural materials that could achieve satisfactory results and minimize adverse effects. Natural polyphenols, named for the multiple phenolic hydroxyl groups in their structures, are promising candidates and continue to be of scientific interest due to their multifunctional biological properties and safety. Polyphenols have a wide range of pharmacological effects. In addition to the most common effect, antioxidation, polyphenols have anti-inflammatory, bacteriostatic, antitumor, and other biological effects associated with reduced risk of a number of chronic diseases. Various polyphenols have also shown efficacy against different types of skin and hair diseases, both in vitro and in vivo, via different mechanisms. Thus, this paper reviews the research progress in natural polyphenols for the protection of skin and hair health, especially focusing on their potential therapeutic mechanisms against skin and hair disorders. A deep understanding of natural polyphenols provides a new perspective for the safe treatment of skin diseases and hair loss.
Collapse
|
|
34
|
Colletti A, Fratter A, Pellizzato M, Cravotto G. Nutraceutical Approaches to Dyslipidaemia: The Main Formulative Issues Preventing Efficacy. Nutrients 2022; 14:nu14224769. [PMID: 36432457 PMCID: PMC9696395 DOI: 10.3390/nu14224769] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 10/29/2022] [Accepted: 11/04/2022] [Indexed: 11/16/2022] Open
Abstract
Currently, the nutraceutical approach to treat dyslipidaemia is increasing in use, and in many cases is used by physicians as the first choice in the treatment of patients with borderline values. Nutraceuticals represent an excellent opportunity to treat the preliminary conditions not yet showing the pathological signs of dyslipidaemia. Their general safety, the patient's confidence, the convincing proof of efficacy and the reasonable costs prompted the market of new preparations. Despite this premise, many nutraceutical products are poorly formulated and do not meet the minimum requirements to ensure efficacy in normalizing blood lipid profiles, promoting cardiovascular protection, and normalizing disorders of glycemic metabolism. In this context, bioaccessibility and bioavailability of the active compounds is a crucial issue. Little attention is paid to the proper formulations needed to improve the overall bioavailability of the active molecules. According to these data, many products prove to be insufficient to ensure full enteric absorption. The present review analysed the literature in the field of nutraceuticals for the treatment of dyslipidemia, focusing on resveratrol, red yeast rice, berberine, and plant sterols, which are among the nutraceuticals with the greatest formulation problems, highlighting bioavailability and the most suitable formulations.
Collapse
Affiliation(s)
- Alessandro Colletti
- Department of Science and Drug Technology, University of Turin, 10124 Turin, Italy
- Italian Society of Nutraceutical Formulators (SIFNut), 31033 Treviso, Italy
| | - Andrea Fratter
- Italian Society of Nutraceutical Formulators (SIFNut), 31033 Treviso, Italy
- Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35122 Padua, Italy
| | - Marzia Pellizzato
- Italian Society of Nutraceutical Formulators (SIFNut), 31033 Treviso, Italy
| | - Giancarlo Cravotto
- Department of Science and Drug Technology, University of Turin, 10124 Turin, Italy
- Italian Society of Nutraceutical Formulators (SIFNut), 31033 Treviso, Italy
- Correspondence: ; Tel.: +39-011-670-7103
| |
Collapse
|
|
35
|
Varo MA, Serratosa MP, Martín-Gómez J, Moyano L, Mérida J. Influence of Fermentation Time on the Phenolic Compounds, Vitamin C, Color and Antioxidant Activity in the Winemaking Process of Blueberry ( Vaccinium corymbosum) Wine Obtained by Maceration. Molecules 2022; 27:7744. [PMID: 36431848 PMCID: PMC9696742 DOI: 10.3390/molecules27227744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 11/07/2022] [Accepted: 11/08/2022] [Indexed: 11/12/2022] Open
Abstract
Flavonoid compounds, including anthocyanins and flavan-3-ol derivatives, total tannins, total vitamin C and resveratrol were analyzed by HPLC in blueberry fruits, their skin and pulp, as well as in wines produced from them. Two wines were elaborated, with different times of fermentation. The fruit analysis provided information on the distribution of bioactive compounds in the berries, showing that the skin had the highest concentrations of all compounds. The winemaking process needed a maceration stage to extract these compounds from skins to wine. This maceration process increased the concentration of all compounds and the antioxidant activity values measured by the DPPH assay, but long maceration times decreased the compounds and the antioxidant activity, due to the phenolic compounds that were involved in several reactions, such as polymerization, copigmentation, degradation, formation of pyranoanthocyanins and reactions between anthocyanins and tannins. The sensorial analysis of wines showed that partial fermentation wine had better characteristics than total fermentation wine, although both wines had a high acidity.
Collapse
Affiliation(s)
- M. Angeles Varo
- Departamento de Química Agrícola, Edafología y Microbiología, Facultad de Ciencias, Campus de Rabanales, Universidad de Córdoba, Ed. Marie Curie, 14014 Córdoba, Spain
| | - Maria P. Serratosa
- Departamento de Química Agrícola, Edafología y Microbiología, Facultad de Ciencias, Campus de Rabanales, Universidad de Córdoba, Ed. Marie Curie, 14014 Córdoba, Spain
| | | | | | | |
Collapse
|
|
36
|
R. M. Metawea O, Teleb M, Haiba NS, Elzoghby AO, Khafaga AF, Noreldin AE, Khattab SN, Khalil HH. Folic acid-poly(N-isopropylacrylamide-maltodextrin) nanohydrogels a novel thermo-/pH-responsive polymer for resveratrol breast cancer targeted therapy. Eur Polym J 2022. [DOI: 10.1016/j.eurpolymj.2022.111721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
|
|
37
|
Bakrim S, El Omari N, El Hachlafi N, Bakri Y, Lee LH, Bouyahya A. Dietary Phenolic Compounds as Anticancer Natural Drugs: Recent Update on Molecular Mechanisms and Clinical Trials. Foods 2022; 11:foods11213323. [PMID: 36359936 PMCID: PMC9657352 DOI: 10.3390/foods11213323] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 10/16/2022] [Accepted: 10/18/2022] [Indexed: 12/05/2022] Open
Abstract
Given the stochastic complexity of cancer diseases, the development of chemotherapeutic drugs is almost limited by problems of selectivity and side effects. Furthermore, an increasing number of protective approaches have been recently considered as the main way to limit these pathologies. Natural bioactive compounds, and particularly dietary phenolic compounds, showed major protective and therapeutic effects against different types of human cancers. Indeed, phenolic substances have functional groups that allow them to exert several anti-cancer mechanisms, such as the induction of apoptosis, autophagy, cell cycle arrest at different stages, and the inhibition of telomerase. In addition, in vivo studies show that these phenolic compounds also have anti-angiogenic effects via the inhibition of invasion and angiogenesis. Moreover, clinical studies have already highlighted certain phenolic compounds producing clinical effects alone, or in combination with drugs used in chemotherapy. In the present work, we present a major advance in research concerning the mechanisms of action of the different phenolic compounds that are contained in food medicinal plants, as well as evidence from the clinical trials that focus on them.
Collapse
Affiliation(s)
- Saad Bakrim
- Geo-Bio-Environment Engineering and Innovation Laboratory, Molecular Engineering, Biotechnology, and Innovation Team, Polydisciplinary Faculty of Taroudant, Ibn Zohr University, Agadir 80000, Morocco
| | - Nasreddine El Omari
- Laboratory of Histology, Embryology, and Cytogenetic, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat 10100, Morocco
| | - Naoufal El Hachlafi
- Microbial Biotechnology and Bioactive Molecules Laboratory, Sciences and Technologies Faculty, Sidi Mohmed Ben Abdellah University, Fes 30000, Morocco
| | - Youssef Bakri
- Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, Mohammed V University in Rabat, Rabat 10106, Morocco
| | - Learn-Han Lee
- Novel Bacteria and Drug Discovery Research Group (NBDD), Microbiome and Bioresource Research Strength (MBRS), Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Subang Jaya 47500, Malaysia
- Correspondence: (L.-H.L.); (A.B.)
| | - Abdelhakim Bouyahya
- Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, Mohammed V University in Rabat, Rabat 10106, Morocco
- Correspondence: (L.-H.L.); (A.B.)
| |
Collapse
|
|
38
|
Kobets T, Smith BPC, Williams GM. Food-Borne Chemical Carcinogens and the Evidence for Human Cancer Risk. Foods 2022; 11:2828. [PMID: 36140952 PMCID: PMC9497933 DOI: 10.3390/foods11182828] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Revised: 09/07/2022] [Accepted: 09/08/2022] [Indexed: 11/16/2022] Open
Abstract
Commonly consumed foods and beverages can contain chemicals with reported carcinogenic activity in rodent models. Moreover, exposures to some of these substances have been associated with increased cancer risks in humans. Food-borne carcinogens span a range of chemical classes and can arise from natural or anthropogenic sources, as well as form endogenously. Important considerations include the mechanism(s) of action (MoA), their relevance to human biology, and the level of exposure in diet. The MoAs of carcinogens have been classified as either DNA-reactive (genotoxic), involving covalent reaction with nuclear DNA, or epigenetic, involving molecular and cellular effects other than DNA reactivity. Carcinogens are generally present in food at low levels, resulting in low daily intakes, although there are some exceptions. Carcinogens of the DNA-reactive type produce effects at lower dosages than epigenetic carcinogens. Several food-related DNA-reactive carcinogens, including aflatoxins, aristolochic acid, benzene, benzo[a]pyrene and ethylene oxide, are recognized by the International Agency for Research on Cancer (IARC) as causes of human cancer. Of the epigenetic type, the only carcinogen considered to be associated with increased cancer in humans, although not from low-level food exposure, is dioxin (TCDD). Thus, DNA-reactive carcinogens in food represent a much greater risk than epigenetic carcinogens.
Collapse
Affiliation(s)
- Tetyana Kobets
- Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA
| | - Benjamin P. C. Smith
- Future Ready Food Safety Hub, Nanyang Technological University, Singapore 639798, Singapore
| | - Gary M. Williams
- Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA
| |
Collapse
|
|
39
|
Xu Q, Liu X, Mohseni G, Hao X, Ren Y, Xu Y, Gao H, Wang Q, Wang Y. Mechanism research and treatment progress of NAD pathway related molecules in tumor immune microenvironment. Cancer Cell Int 2022; 22:242. [PMID: 35906622 PMCID: PMC9338646 DOI: 10.1186/s12935-022-02664-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 07/19/2022] [Indexed: 11/21/2022] Open
Abstract
Nicotinamide adenine dinucleotide (NAD) is the core of cellular energy metabolism. NAMPT, Sirtuins, PARP, CD38, and other molecules in this classic metabolic pathway affect many key cellular functions and are closely related to the occurrence and development of many diseases. In recent years, several studies have found that these molecules can regulate cell energy metabolism, promote the release of related cytokines, induce the expression of neoantigens, change the tumor immune microenvironment (TIME), and then play an anticancer role. Drugs targeting these molecules are under development or approved for clinical use. Although there are some side effects and drug resistance, the discovery of novel drugs, the development of combination therapies, and the application of new technologies provide solutions to these challenges and improve efficacy. This review presents the mechanisms of action of NAD pathway-related molecules in tumor immunity, advances in drug research, combination therapies, and some new technology-related therapies.
Collapse
Affiliation(s)
- QinChen Xu
- Department of Clinical Laboratory, The Second Hospital of Shandong University, 247 Beiyuan Street, 250033, Jinan, Shandong, China
| | - Xiaoyan Liu
- Department of Clinical Laboratory, The Second Hospital of Shandong University, 247 Beiyuan Street, 250033, Jinan, Shandong, China
| | - Ghazal Mohseni
- Department of Clinical Laboratory, The Second Hospital of Shandong University, 247 Beiyuan Street, 250033, Jinan, Shandong, China
| | - Xiaodong Hao
- Department of Clinical Laboratory, The Second Hospital of Shandong University, 247 Beiyuan Street, 250033, Jinan, Shandong, China
| | - Yidan Ren
- Department of Clinical Laboratory, The Second Hospital of Shandong University, 247 Beiyuan Street, 250033, Jinan, Shandong, China
| | - Yiwei Xu
- Marine College, Shandong University, 264209, Weihai, China
| | - Huiru Gao
- Department of Clinical Laboratory, The Second Hospital of Shandong University, 247 Beiyuan Street, 250033, Jinan, Shandong, China
| | - Qin Wang
- Department of Anesthesiology, Cheeloo College of Medicine, Qilu Hospital, Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong, China.
| | - Yunshan Wang
- Department of Clinical Laboratory, The Second Hospital of Shandong University, 247 Beiyuan Street, 250033, Jinan, Shandong, China.
| |
Collapse
|
|
40
|
Saleem Z, Rehman K, Hamid Akash MS. Role of Drug Delivery System in Improving the Bioavailability of Resveratrol. Curr Pharm Des 2022; 28:1632-1642. [DOI: 10.2174/1381612828666220705113514] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 03/29/2022] [Indexed: 11/22/2022]
Abstract
Abstract:
Resveratrol (RSV) is known as a natural polyphenolic compound that is known for its therapeutic activities but has limited bioavailability. The aim of our study was to explore various drug-delivering methods that are being employed to achieve target-oriented delivery and therapeutic performance of RSV. To improve the bioavailability and pharmacokinetic properties of RSV, efforts are being made by producing efficient formulations accompanying efficient drug delivery strategies. Several clinical trial studies have been conducted on RSV isomers, and the majority of studies indicated that trans-RSV had better clinical potential and therapeutic effectiveness in various types of complications such as colorectal cancer, metabolic syndrome, hypertension, obesity, neurodegenerative diseases, diabetes, hepatic disease, cardiac disorders, and breast cancer. However, multiple research studies enable us to understand various strategies that can enhance the systemic availability and efficacy of topical RSV formulations. In this article, we emphasize the hurdles of RSV delivery processes. We summarized that for delivering liquid and solid microparticles of RSV, the micro-particulate system works efficiently. Another technique in which particles are enclosed by a coating is called microencapsulation. This technique reduces the degradation of pharmaceutical compounds. Similarly, the cyclodextrin system is mainly used for poorly soluble drugs. On the other hand, the vesicular system is another micro-particulate system that can encapsulate hydrophilic and hydrophobic drugs. However, the RSV nanosponge formulations have advanced nanodrug delivery systems also make it possible to use RSV for its antioxidant potential.
Collapse
Affiliation(s)
- Zonish Saleem
- Department of Pharmaceutical Chemistry, Government College University Faisalabad, Pakistan
| | - Kanwal Rehman
- Department of Pharmacy, The Women University, Multan, Pakistan
| | | |
Collapse
|
|
41
|
Bajalia EM, Azzouz FB, Chism DA, Giansiracusa DM, Wong CG, Plaskett KN, Bishayee A. Phytochemicals for the Prevention and Treatment of Renal Cell Carcinoma: Preclinical and Clinical Evidence and Molecular Mechanisms. Cancers (Basel) 2022; 14:3278. [PMID: 35805049 PMCID: PMC9265746 DOI: 10.3390/cancers14133278] [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: 05/23/2022] [Revised: 06/26/2022] [Accepted: 06/30/2022] [Indexed: 11/18/2022] Open
Abstract
Renal cell carcinoma (RCC) is associated with about 90% of renal malignancies, and its incidence is increasing globally. Plant-derived compounds have gained significant attention in the scientific community for their preventative and therapeutic effects on cancer. To evaluate the anticancer potential of phytocompounds for RCC, we compiled a comprehensive and systematic review of the available literature. Our work was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. The literature search was performed using scholarly databases such as PubMed, Scopus, and ScienceDirect and keywords such as renal cell carcinoma, phytochemicals, cancer, tumor, proliferation, apoptosis, prevention, treatment, in vitro, in vivo, and clinical studies. Based on in vitro results, various phytochemicals, such as phenolics, terpenoids, alkaloids, and sulfur-containing compounds, suppressed cell viability, proliferation and growth, showed cytotoxic activity, inhibited invasion and migration, and enhanced the efficacy of chemotherapeutic drugs in RCC. In various animal tumor models, phytochemicals suppressed renal tumor growth, reduced tumor size, and hindered angiogenesis and metastasis. The relevant antineoplastic mechanisms involved upregulation of caspases, reduction in cyclin activity, induction of cell cycle arrest and apoptosis via modulation of a plethora of cell signaling pathways. Clinical studies demonstrated a reduced risk for the development of kidney cancer and enhancement of the efficacy of chemotherapeutic drugs. Both preclinical and clinical studies displayed significant promise of utilizing phytochemicals for the prevention and treatment of RCC. Further research, confirming the mechanisms and regulatory pathways, along with randomized controlled trials, are needed to establish the use of phytochemicals in clinical practice.
Collapse
Affiliation(s)
| | | | | | | | | | | | - Anupam Bishayee
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA; (E.M.B.); (F.B.A.); (D.A.C.); (D.M.G.); (C.G.W.); (K.N.P.)
| |
Collapse
|
|
42
|
Hong W, Wang B, Zhu Y, Wu J, Qiu L, Ling S, Zhou Z, Dai Y, Zhong Z, Zheng Y. Female germline stem cells: aging and anti-aging. J Ovarian Res 2022; 15:79. [PMID: 35787298 PMCID: PMC9251950 DOI: 10.1186/s13048-022-01011-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Accepted: 06/17/2022] [Indexed: 01/17/2023] Open
Abstract
The delay of ovarian aging and the fertility preservation of cancer patients are the eternal themes in the field of reproductive medicine. Acting as the pacemaker of female physiological aging, ovary is also considered as the principle player of cancer, cardiovascular diseases, cerebrovascular diseases, neurodegenerative diseases and etc. However, its aging mechanism and preventive measures are still unclear. Some researchers attempt to activate endogenous ovarian female germline stem cells (FGSCs) to restore ovarian function, as the most promising approach. FGSCs are stem cells in the adult ovaries that can be infinitely self-renewing and have the potential of committed differention. This review aims to elucidate FGSCs aging mechanism from multiple perspectives such as niches, immune disorder, chronic inflammation and oxidative stress. Therefore, the rebuilding nichs of FGSCs, regulation of immune dysfunction, anti-inflammation and oxidative stress remission are expected to restore or replenish FGSCs, ultimately to delay ovarian aging.
Collapse
Affiliation(s)
- Wenli Hong
- Reproductive Health Department, Shenzhen Traditional Chinese Medicine Hospital, the Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen, Guangdong, 518000, People's Republic of China.,Shenzhen University Health Science Center, Shenzhen, Guangdong, 518000, People's Republic of China
| | - Baofeng Wang
- ARTcenter, Shenzhen Hengsheng Hospital, Shenzhen, Guangdong, 518000, People's Republic of China
| | - Yasha Zhu
- Reproductive Health Department, Shenzhen Traditional Chinese Medicine Hospital, the Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen, Guangdong, 518000, People's Republic of China
| | - Jun'e Wu
- Reproductive Health Department, Shenzhen Traditional Chinese Medicine Hospital, the Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen, Guangdong, 518000, People's Republic of China
| | - Li Qiu
- Reproductive Health Department, Shenzhen Traditional Chinese Medicine Hospital, the Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen, Guangdong, 518000, People's Republic of China
| | - Shuyi Ling
- Reproductive Health Department, Shenzhen Traditional Chinese Medicine Hospital, the Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen, Guangdong, 518000, People's Republic of China
| | - Ziqiong Zhou
- Reproductive Health Department, Shenzhen Traditional Chinese Medicine Hospital, the Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen, Guangdong, 518000, People's Republic of China
| | - Yuqing Dai
- Reproductive Health Department, Shenzhen Traditional Chinese Medicine Hospital, the Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen, Guangdong, 518000, People's Republic of China
| | - Zhisheng Zhong
- Reproductive Health Department, Shenzhen Traditional Chinese Medicine Hospital, the Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen, Guangdong, 518000, People's Republic of China.
| | - Yuehui Zheng
- Reproductive Health Department, Shenzhen Traditional Chinese Medicine Hospital, the Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen, Guangdong, 518000, People's Republic of China.
| |
Collapse
|
|
43
|
Roshani M, Jafari A, Loghman A, Sheida AH, Taghavi T, Tamehri Zadeh SS, Hamblin MR, Homayounfal M, Mirzaei H. Applications of resveratrol in the treatment of gastrointestinal cancer. Biomed Pharmacother 2022; 153:113274. [PMID: 35724505 DOI: 10.1016/j.biopha.2022.113274] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 05/28/2022] [Accepted: 06/08/2022] [Indexed: 12/15/2022] Open
Abstract
Natural product compounds have lately attracted interest in the scientific community as a possible treatment for gastrointestinal (GI) cancer, due to their anti-inflammatory and anticancer properties. There are many preclinical, clinical, and epidemiological studies, suggesting that the consumption of polyphenol compounds, which are abundant in vegetables, grains, fruits, and pulses, may help to prevent various illnesses and disorders from developing, including several GI cancers. The development of GI malignancies follows a well-known path, in which normal gastrointestinal cells acquire abnormalities in their genetic composition, causing the cells to continuously proliferate, and metastasize to other sites, especially the brain and liver. Natural compounds with the ability to affect oncogenic pathways might be possible treatments for GI malignancies, and could easily be tested in clinical trials. Resveratrol is a non-flavonoid polyphenol and a natural stilbene, acting as a phytoestrogen with anti-cancer, cardioprotective, anti-oxidant, and anti-inflammatory properties. Resveratrol has been shown to overcome resistance mechanisms in cancer cells, and when combined with conventional anticancer drugs, could sensitize cancer cells to chemotherapy. Several new resveratrol analogs and nanostructured delivery vehicles with improved anti-GI cancer efficacy, absorption, and pharmacokinetic profiles have already been developed. This present review focuses on the in vitro and in vivo effects of resveratrol on GI cancers, as well as the underlying molecular mechanisms of action.
Collapse
Affiliation(s)
- Mohammad Roshani
- Internal Medicine and Gastroenterology, Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Ameneh Jafari
- Advanced Therapy Medicinal Product (ATMP) Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran; Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Amir Hossein Sheida
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran; Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | | | | | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein 2028, South Africa
| | - Mina Homayounfal
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
| |
Collapse
|
|
44
|
Levenson AS. Metastasis-associated protein 1-mediated antitumor and anticancer activity of dietary stilbenes for prostate cancer chemoprevention and therapy. Semin Cancer Biol 2022; 80:107-117. [PMID: 32126261 PMCID: PMC7483334 DOI: 10.1016/j.semcancer.2020.02.012] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 02/17/2020] [Accepted: 02/18/2020] [Indexed: 02/07/2023]
Abstract
Dietary bioactive polyphenols that demonstrate beneficial biological functions including antioxidant, anti-inflammatory, and anticancer activity hold immense promise as effective and safe chemopreventive and chemosensitizing natural anticancer agents. The underlying molecular mechanisms of polyphenols' multiple effects are complex and these molecules are considered promising targets for chemoprevention and therapy. However, the development of novel personalized targeted chemopreventive and therapeutic strategies is essential for successful therapeutic outcomes. In this review, we highlight the potential of metastasis-associated protein 1 (MTA1)-targeted anticancer and antitumor effects of three dietary stilbenes, namely resveratrol, pterostilbene, and gnetin C, for prostate cancer management. MTA1, an epigenetic reader and master transcriptional regulator, plays a key role in all stages of prostate cancer progression and metastasis. Stilbenes inhibit MTA1 expression, disrupt the MTA1/histone deacetylase complex, modulate MTA1-associated Epi-miRNAs and reduce MTA1-dependent inflammation, cell survival, and metastasis in prostate cancer in vitro and in vivo. Overall, the MTA1-targeted strategies involving dietary stilbenes may be valuable for effective chemoprevention in selected subpopulations of early stage prostate cancer patients and for combinatorial strategies with conventional chemotherapeutic drugs against advanced metastatic prostate cancer.
Collapse
Affiliation(s)
- Anait S Levenson
- Department of Biomedical Sciences, School of Veterinary Medicine, Long Island University, Brookville, NY, 11548, USA.
| |
Collapse
|
|
45
|
Tewari D, Priya A, Bishayee A, Bishayee A. Targeting transforming growth factor-β signalling for cancer prevention and intervention: Recent advances in developing small molecules of natural origin. Clin Transl Med 2022; 12:e795. [PMID: 35384373 PMCID: PMC8982327 DOI: 10.1002/ctm2.795] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Revised: 03/12/2022] [Accepted: 03/16/2022] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Cancer is the world's second leading cause of death, but a significant advancement in cancer treatment has been achieved within the last few decades. However, major adverse effects and drug resistance associated with standard chemotherapy have led towards targeted treatment options. OBJECTIVES Transforming growth factor-β (TGF-β) signaling plays a key role in cell proliferation, differentiation, morphogenesis, regeneration, and tissue homeostasis. The prime objective of this review is to decipher the role of TGF-β in oncogenesis and to evaluate the potential of various natural and synthetic agents to target this dysregulated pathway to confer cancer preventive and anticancer therapeutic effects. METHODS Various authentic and scholarly databases were explored to search and obtain primary literature for this study. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) criteria was followed for the review. RESULTS Here we provide a comprehensive and critical review of recent advances on our understanding of the effect of various bioactive natural molecules on the TGF-β signaling pathway to evaluate their full potential for cancer prevention and therapy. CONCLUSION Based on emerging evidence as presented in this work, TGF-β-targeting bioactive compounds from natural sources can serve as potential therapeutic agents for prevention and treatment of various human malignancies.
Collapse
Affiliation(s)
- Devesh Tewari
- Department of PharmacognosySchool of Pharmaceutical SciencesLovely Professional UniversityPhagwaraPunjabIndia
| | - Anu Priya
- Department of PharmacologySchool of Pharmaceutical SciencesLovely Professional UniversityPhagwaraPunjabIndia
| | | | - Anupam Bishayee
- College of Osteopathic MedicineLake Erie College of Osteopathic MedicineBradentonFloridaUSA
| |
Collapse
|
|
46
|
Islam MR, Islam F, Nafady MH, Akter M, Mitra S, Das R, Urmee H, Shohag S, Akter A, Chidambaram K, Alhumaydhi FA, Emran TB, Cavalu S. Natural Small Molecules in Breast Cancer Treatment: Understandings from a Therapeutic Viewpoint. Molecules 2022; 27:2165. [PMID: 35408561 PMCID: PMC9000328 DOI: 10.3390/molecules27072165] [Citation(s) in RCA: 82] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 03/21/2022] [Accepted: 03/23/2022] [Indexed: 12/12/2022] Open
Abstract
Breast cancer (BrCa) is the most common malignancy in women and the second most significant cause of death from cancer. BrCa is one of the most challenging malignancies to treat, and it accounts for a large percentage of cancer-related deaths. The number of cases requiring more effective BrCa therapy has increased dramatically. Scientists are looking for more productive agents, such as organic combinations, for BrCa prevention and treatment because most chemotherapeutic agents are linked to cancer metastasis, the resistance of the drugs, and side effects. Natural compounds produced by living organisms promote apoptosis and inhibit metastasis, slowing the spread of cancer. As a result, these compounds may delay the spread of BrCa, enhancing survival rates and reducing the number of deaths caused by BrCa. Several natural compounds inhibit BrCa production while lowering cancer cell proliferation and triggering cell death. Natural compounds, in addition to therapeutic approaches, are efficient and potential agents for treating BrCa. This review highlights the natural compounds demonstrated in various studies to have anticancer properties in BrCa cells. Future research into biological anti-BrCa agents may pave the way for a new era in BrCa treatment, with natural anti-BrCa drugs playing a key role in improving BrCa patient survival rates.
Collapse
Affiliation(s)
- Md. Rezaul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh; (M.R.I.); (F.I.); (M.A.); (A.A.)
| | - Fahadul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh; (M.R.I.); (F.I.); (M.A.); (A.A.)
| | - Mohamed H. Nafady
- Faculty of Applied Health Science Technology, Misr University for Science and Technology, Giza 12568, Egypt;
| | - Muniya Akter
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh; (M.R.I.); (F.I.); (M.A.); (A.A.)
| | - Saikat Mitra
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh; (S.M.); (R.D.)
| | - Rajib Das
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh; (S.M.); (R.D.)
| | - Humaira Urmee
- Department of Pharmaceutical Science, North South University, Dhaka 1229, Bangladesh;
| | - Sheikh Shohag
- Department of Biochemistry and Molecular Biology, Faculty of Life Science, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh;
| | - Aklima Akter
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh; (M.R.I.); (F.I.); (M.A.); (A.A.)
| | - Kumarappan Chidambaram
- Department of Pharmacology and Toxicology, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia;
| | - Fahad A. Alhumaydhi
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 52571, Saudi Arabia;
| | - Talha Bin Emran
- Department of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, Bangladesh
| | - Simona Cavalu
- Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania
| |
Collapse
|
|
47
|
Kim SH, Lee YC. Plant-Derived Nanoscale-Encapsulated Antioxidants for Oral and Topical Uses: A Brief Review. Int J Mol Sci 2022; 23:ijms23073638. [PMID: 35409001 PMCID: PMC8998173 DOI: 10.3390/ijms23073638] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Revised: 03/23/2022] [Accepted: 03/24/2022] [Indexed: 02/04/2023] Open
Abstract
Several plant-based nanoscale-encapsulated antioxidant compounds (rutin, myricetin, β-carotene, fisetin, lycopene, quercetin, genkwanin, lutein, resveratrol, eucalyptol, kaempferol, glabridin, pinene, and whole-plant bio-active compounds) are briefly introduced in this paper, along with their characteristics. Antioxidants’ bioavailability has become one of the main research topics in bio-nanomedicine. Two low patient compliance drug delivery pathways (namely, the oral and topical delivery routes), are described in detail in this paper, for nanoscale colloidal systems and gel formulations. Both routes and/or formulations seek to improve bioavailability and maximize the drug agents’ efficiency. Some well-known compounds have been robustly studied, but many remain elusive. The objective of this review is to discuss recent studies and advantages of nanoscale formulations of plant-derived antioxidant compounds.
Collapse
|
|
48
|
Choi CY, Lim SC, Lee TB, Han SI. Molecular Basis of Resveratrol-Induced Resensitization of Acquired Drug-Resistant Cancer Cells. Nutrients 2022; 14:nu14030699. [PMID: 35277058 PMCID: PMC8838003 DOI: 10.3390/nu14030699] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Revised: 01/28/2022] [Accepted: 02/01/2022] [Indexed: 02/07/2023] Open
Abstract
Multidrug resistance (MDR) to anticancer drugs remains a serious obstacle to the success of cancer chemotherapy. Resveratrol, a polyphenol, present in natural products exerts anticancer activity and acts as a potential MDR inhibitor in various drug-resistant cancer cells. In the process of resensitization of drug-resistant cancer cells, resveratrol has been shown to interfere with ABC transporters and drug-metabolizing enzymes, increase DNA damage, inhibit cell cycle progression, and induce apoptosis and autophagy, as well as prevent the induction of epithelial to mesenchymal transition (EMT) and cancer stem cells (CSCs). This review summarizes the mechanisms by which resveratrol counteracts MDR in acquired drug-resistant cancer cell lines and provides a critical basis for understanding the regulation of MDR as well as the development of MDR-inhibiting drugs.
Collapse
Affiliation(s)
- Chul Yung Choi
- Department of Biomedical Science, College of Natural Science, Chosun University, Gwangju 61452, Korea;
| | - Sung-Chul Lim
- Department of Pathology, College of Medicine, Chosun University, Gwangju 61452, Korea;
| | - Tae-Bum Lee
- Division of Premedical Science, College of Medicine, Chosun University, Gwangju 61452, Korea;
| | - Song Iy Han
- Division of Premedical Science, College of Medicine, Chosun University, Gwangju 61452, Korea;
- Correspondence: ; Tel.: +82-62-230-6194; Fax: +82-62-226-5860
| |
Collapse
|
|
49
|
Dobrzyńska MM, Gajowik A. Protection and Mitigation by Resveratrol of DNA Damage Induced in Irradiated Human Lymphocytes In Vitro. Radiat Res 2022; 197:149-156. [PMID: 34724059 DOI: 10.1667/rade-20-00037.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 08/30/2021] [Indexed: 11/03/2022]
Abstract
The aim of this study was to examine the protective and/or mitigative properties of resveratrol (RSV) administered before or after irradiation of human lymphocytes in vitro. The isolated lymphocytes were incubated for 1 h with resveratrol, at doses of 0.1 (lowest), 0.5 (medium) or 1 (highest) mM/ml: 1 h before; immediately before; immediately after irradiation; and 1 h after irradiation with 0.5, 1 and 2 Gy. The degree of DNA damage was evaluated by Comet Assay. Treatment of human lymphocytes with resveratrol 1 h before or immediately after radiation exposure showed protection from radiation-induced DNA damage. However, 1 Gy irradiation + 1 mM/ml RSV, and 2 Gy irradiation + 0.5 and 1 mM/ml RSV 1 h before irradiation did not provide the same protection. Significant dose-dependent reduction of the level of DNA damage was observed after application of RSV immediately postirradiation or 1 h postirradiation. The reduction in DNA damage was the highest at the 0.1 dose of resveratrol. Our results lead to the conclusion that resveratrol may act both as a radioprotector as well as a radiomitigator. Resveratrol at the lowest (0.5 mM/ml) dose was more effective when combined with 0.5 and 1 Gy doses of radiation.
Collapse
Affiliation(s)
- Małgorzata M Dobrzyńska
- National Institute of Public Health NIH - National Research Institute, Department of Radiation Hygiene and Radiobiology, 00-791 Warsaw, Poland
| | - Aneta Gajowik
- National Institute of Public Health NIH - National Research Institute, Department of Radiation Hygiene and Radiobiology, 00-791 Warsaw, Poland
| |
Collapse
|
|
50
|
The effect of resveratrol and quercetin intervention on azoxymethane-induced colon cancer in Rats model. CLINICAL NUTRITION OPEN SCIENCE 2022. [DOI: 10.1016/j.nutos.2022.01.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
|