ArticleBMC complementary and alternative medicine2011
Down-regulation of estrogen receptor-alpha and rearranged during transfection tyrosine kinase is associated with withaferin a-induced apoptosis in MCF-7 breast cancer cells.
Article in BMC complementary and alternative medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 81 citations in OpenAlex.
- Ashwagandha (Withania Somnifera): a comprehensive narrative review of its role in enhancing physical performance and health.Nutrition & metabolism · 2026Review
- Mechanisms and potential therapeutic strategies of withaferin A in breast cancer.Pharmacological reports : PR · 2025Review
- Unraveling the role of withanolides as key modulators in breast cancer mitigation.Molecular biology reports · 2025Review
- Article
- Ashwagandha-Induced Programmed Cell Death in the Treatment of Breast Cancer.Current issues in molecular biology · 2024Review
- Phyto-therapeutics as anti-cancer agents in breast cancer: Pathway targeting and mechanistic elucidation.Saudi journal of biological sciences · 2024Review
- The Therapeutic Effects of Withaferin A against Cancer: Overview and Updates.Current molecular medicine · 2024Review
- Withanolide derivatives: natural compounds with anticancer potential offer low toxicity to fertility and ovarian follicles in mice.Animal reproduction · 2024Article
- Withaferin A: A Pleiotropic Anticancer Agent from the Indian Medicinal PlantPharmaceuticals (Basel, Switzerland) · 2023Review
- Withaferin A: A Dietary Supplement with Promising Potential as an Anti-Tumor Therapeutic for Cancer Treatment - Pharmacology and Mechanisms.Drug design, development and therapy · 2023Review
- The use of African medicinal plants in cancer management.Frontiers in pharmacology · 2023Review
- Review
- Evaluating anticancer properties of Withaferin A-a potent phytochemical.Frontiers in pharmacology · 2022Review
- Withaferin A: From Ancient Remedy to Potential Drug Candidate.Molecules (Basel, Switzerland) · 2021Review
- Withaferin A Triggers Apoptosis and DNA Damage in Bladder Cancer J82 Cells through Oxidative Stress.Antioxidants (Basel, Switzerland) · 2021Article
- Perspectives on natural compounds in chemoprevention and treatment of cancer: an update with new promising compounds.European journal of cancer (Oxford, England : 1990) · 2021Review
- The Potential Role of Nutraceuticals as an Adjuvant in Breast Cancer Patients to Prevent Hair Loss Induced by Endocrine Therapy.Nutrients · 2020Review
- A Comprehensive Review and Perspective on Anticancer Mechanisms of Withaferin A in Breast Cancer.Cancer prevention research (Philadelphia, Pa.) · 2020Review
- Bioactive Compounds: Multi-Targeting Silver Bullets for Preventing and Treating Breast Cancer.Cancers · 2019Review
- Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundWithaferin A (WA), a naturally occurring withanolide, induces apoptosis in both estrogen-responsive MCF-7 and estrogen-independent MDA-MB-231 breast cancer cell lines with higher sensitivity in MCF-7 cells, but the underlying mechanisms are not well defined. The purpose of this study was to determine the anti-cancer effects of WA in MCF-7 breast cancer cells and explore alterations in estrogen receptor alpha (ERα) and its associated molecules in vitro as novel mechanisms of WA action.
methodsThe effects of WA on MCF-7 viability and proliferation were evaluated by 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and trypan blue exclusion assays. Apoptosis was evaluated by Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) flow cytometry and Western blot analysis of poly (ADP-ribose) polymerase (PARP) cleavage. Cell cycle effects were analyzed by PI flow cytometry. Western blotting was also conducted to examine alterations in the expression of ERα and pathways that are associated with ERα function.
resultsWA resulted in growth inhibition and decreased viability in MCF-7 cells with an IC50 of 576 nM for 72 h. It also caused a dose- and time-dependent apoptosis and G2/M cell cycle arrest. WA-induced apoptosis was associated with down-regulation of ERα, REarranged during Transfection (RET) tyrosine kinase, and heat shock factor-1 (HSF1), as well as up-regulation of phosphorylated p38 mitogen-activated protein kinase (phospho-p38 MAPK), p53 and p21 protein expression. Co-treatment with protein synthesis inhibitor cycloheximide or proteasome inhibitor MG132 revealed that depletion of ERα by WA is post-translational, due to proteasome-dependent ERα degradation.
conclusionsTaken together, down-regulation of ERα, RET, HSF1 and up-regulation of phospho-p38 MAPK, p53, p21 are involved in the pro-apoptotic and growth-inhibitory effects of WA in MCF-7 breast cancer cells in vitro. Down-regulation of ERα protein levels by WA is caused by proteasome-dependent ERα degradation.
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