ArticleMolecular carcinogenesis2014
Role of mitogen-activated protein kinases and Mcl-1 in apoptosis induction by withaferin A in human breast cancer cells.
Article in Molecular carcinogenesis, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 65 citations in OpenAlex.
- Exploring the therapeutic potential of withaferin A by modulating key oncosignaling pathways.Naunyn-Schmiedeberg's archives of pharmacology · 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
- Deciphering the multi-scale mechanism of herbal phytoconstituents in targeting breast cancer: a computational pharmacological perspective.Scientific reports · 2024Article
- Ashwagandha-Induced Programmed Cell Death in the Treatment of Breast Cancer.Current issues in molecular biology · 2024Review
- The Therapeutic Effects of Withaferin A against Cancer: Overview and Updates.Current molecular medicine · 2024Review
- Therapeutic and pharmacological efficacy of plant-derived bioactive compounds in targeting breast cancer.American journal of translational research · 2024Review
- Withaferin A: A Pleiotropic Anticancer Agent from the Indian Medicinal PlantPharmaceuticals (Basel, Switzerland) · 2023Review
- Withaferin A Inhibits Fatty Acid Synthesis in Rat Mammary Tumors.Cancer prevention research (Philadelphia, Pa.) · 2023Article
- 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
- Withaferin A Inhibits Neutrophil Adhesion, Migration, and Respiratory Burst and Promotes Timely Neutrophil Apoptosis.Frontiers in veterinary science · 2022Article
- Article
- Critical review of theBulletin of the National Research Centre · 2021Review
- Tackling Chronic Inflammation with Withanolide Phytochemicals-A Withaferin a Perspective.Antioxidants (Basel, Switzerland) · 2020Review
- A Comprehensive Review and Perspective on Anticancer Mechanisms of Withaferin A in Breast Cancer.Cancer prevention research (Philadelphia, Pa.) · 2020Review
- Withaferin A-mediated apoptosis in breast cancer cells is associated with alterations in mitochondrial dynamics.Mitochondrion · 2019Article
- Cancer-associated fibroblasts contribute to cisplatin resistance by modulating ANXA3 in lung cancer cells.Cancer science · 2019Article
- Targeting claudin-3 suppresses stem cell-like phenotype in nonsquamous non-small-cell lung carcinoma.Lung cancer management · 2019Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Withaferin A (WA), a bioactive constituent of Ayurvedic medicine plant Withania somnifera, is a potent apoptosis inducer in cancer cells but the mechanism of cell death induction is not fully characterized. The present study was undertaken to determine the role of mitogen-activated protein kinases (MAPK), including c-jun NH2 -terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 MAPK, and anti-apoptotic protein myeloid cell leukemia-1 (Mcl-1) in regulation of WA-induced apoptosis using human breast cancer cells. Exposure of MCF-7 (estrogen responsive) and SUM159 (triple negative) human breast cancer cells to WA resulted in increased phosphorylation of ERK, JNK, and p38 MAPK, but these effects were relatively more pronounced in the former cell line than in SUM159. Overexpression of manganese-superoxide dismutase conferred partial protection against WA-mediated hyperphosphorylation of ERK, but not JNK or p38 MAPK. Cell death resulting from WA treatment in MCF-7 cells was significantly augmented by pharmacological inhibition of ERK and p38 MAPK. Interestingly, the WA-induced apoptosis in MCF-7 cells was partially but significantly blocked in the presence of a JNK-specific inhibitor. Pharmacological inhibition of ERK or JNK had no effect on WA-induced apoptosis in SUM159 cells. The WA-treated cells exhibited induction of long and short forms of Mcl-1. RNA interference of Mcl-1 alone triggered apoptosis. Furthermore, the WA-induced cell death in MCF-7 cells was modestly but significantly augmented by knockdown of the Mcl-1 protein. These observations indicate that: MAPK have cell line-specific role in cell death by WA, and Mcl-1 induction confers modest protection against WA-induced apoptosis.
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