ArticleCarcinogenesis2019
Withaferin A inhibits lysosomal activity to block autophagic flux and induces apoptosis via energetic impairment in breast cancer cells.
Article in Carcinogenesis, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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Who cites it
26 citing papers in PubMed, 46 citations in OpenAlex.
- Spermine Oxidase Serves as a Key Functional Node in Microbial Dysbiosis-Induced Breast Carcinogenesis.Cancer research · 2026Article
- A pro-carcinogenic oral microbe internalized by breast cancer cells promotes mammary tumorigenesis.Cell communication and signaling : CCS · 2026Article
- Mechanisms and potential therapeutic strategies of withaferin A in breast cancer.Pharmacological reports : PR · 2025Review
- Radiosensitizing effects of Withaferin A in gastric cancer cells via autophagy Inhibition and mitochondrial disruption.Scientific reports · 2025Article
- Herbal Medicine in Breast Cancer Therapy: Mechanisms, Evidence, and Future Perspectives.Current issues in molecular biology · 2025Review
- 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
- Withaferin A and Celastrol Overwhelm Proteostasis.International journal of molecular sciences · 2023Review
- Bioinformatics driven discovery of small molecule compounds that modulate the FOXM1 and PPARA pathway activities in breast cancer.The pharmacogenomics journal · 2023Article
- Review
- Autophagic mechanisms in longevity intervention: role of natural active compounds.Expert reviews in molecular medicine · 2023Review
- 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
- Protective Effect ofFoods (Basel, Switzerland) · 2022Article
- Novel molecules as the emerging trends in cancer treatment: an update.Medical oncology (Northwood, London, England) · 2022Review
- Combination of Ashwagandha Water Extract and Intermittent Fasting as a Therapy to Overcome Cisplatin Resistance in Breast Cancer: AnFrontiers in nutrition · 2022Article
- Article
- Exploring the Multifaceted Therapeutic Potential of Withaferin A and Its Derivatives.Biomedicines · 2020Review
- A Comprehensive Review and Perspective on Anticancer Mechanisms of Withaferin A in Breast Cancer.Cancer prevention research (Philadelphia, Pa.) · 2020Review
- Overview of the anticancer activity of withaferin A, an active constituent of the Indian ginseng Withania somnifera.Environmental science and pollution research international · 2020Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Withaferin A (WFA), a steroidal lactone, negatively regulates breast cancer growth however, its mechanisms of action remain largely elusive. We found that WFA blocks autophagy flux and lysosomal proteolytic activity in breast cancer cells. WFA increases accumulation of autophagosomes, LC3B-II conversion, expression of autophagy-related proteins and autophagosome/lysosome fusion. Autolysosomes display the characteristics of acidic compartments in WFA-treated cells; however, the protein degradation activity of lysosomes is inhibited. Blockade of autophagic flux reduces the recycling of cellular fuels leading to insufficient substrates for tricarboxylic acid (TCA) cycle and impaired oxidative phosphorylation. WFA decreases expression and phosphorylation of lactate dehydrogenase, the key enzyme that catalyzes pyruvate-to-lactate conversion, reduces adenosine triphosphate levels and increases AMP-activated protein kinase (AMPK) activation. AMPK inhibition abrogates while AMPK activation potentiates WFA's effect. WFA and 2-deoxy-d-glucose combination elicits synergistic inhibition of breast cancer cells. Genetic knockout of BECN1 and ATG7 fails to rescue cells from WFA treatment; in contrast, addition of methyl pyruvate to supplement TCA cycle protects WFA-treated cells. Together, these results implicate that WFA is a potent lysosomal inhibitor; energetic impairment is required for WFA-induced apoptosis and growth inhibition and combining WFA and 2-DG is a promising therapeutic strategy for breast cancer.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.