ArticleBiochemical pharmacology2010
Withaferin A targets heat shock protein 90 in pancreatic cancer cells.
Article in Biochemical pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
133 citing papers in PubMed, 307 citations in OpenAlex.
- Heat Shock Protein 90: From Molecular Chaperone Function to Therapeutic Targeting in Malignancies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Evolution of Hsp90 targeting: From stress biology to clinical translation.Cell stress & chaperones · 2026Review
- Exploring the therapeutic potential of withaferin A by modulating key oncosignaling pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Attempts to Achieve Targeted Covalent Inhibition of Hsp90β.Chemical biology & drug design · 2026Article
- Withaferin A inhibits EBV-driven lymphomagenesis through multiple mechanisms, including EBNA1 degradation.Blood · 2026Article
- Ashwagandha (Withania Somnifera): a comprehensive narrative review of its role in enhancing physical performance and health.Nutrition & metabolism · 2026Review
- A Narrative Review on Unravelling Bacterial-Mediated Carcinogenesis and Possible Alternative Treatment Strategies.BioMed research international · 2026Review
- Beyond cytotoxicity: molecular mechanisms of natural products as multi-targeting modulators and chemo-sensitizers in oncology.Frontiers in pharmacology · 2026Review
- Role of HSP90 in Type 2 Diabetes Mellitus and Its Association with Liver Diseases.Molecular biotechnology · 2025Review
- Review
- Chemoproteomics reveals proteome-wide covalent and non-covalent targets of withaferin A.Acta pharmacologica Sinica · 2025Article
- Current mechanistic insights into Withaferin A: a promising potential adjuvant anticancer agent from Withania somnifera.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Synergistic Inhibition of Pancreatic Cancer Cell Growth and Migration by Gemcitabine and Withaferin A.Biomolecules · 2024Article
- Discovery of new Hsp90-Cdc37 protein-protein interaction inhibitors:RSC advances · 2024Article
- FRET Assays for the Identification ofPharmaceuticals (Basel, Switzerland) · 2024Article
- Heat Shock Response and Heat Shock Proteins: Current Understanding and Future Opportunities in Human Diseases.International journal of molecular sciences · 2024Review
- Phyto-therapeutics as anti-cancer agents in breast cancer: Pathway targeting and mechanistic elucidation.Saudi journal of biological sciences · 2024Review
- Bortezomib in Combination with Physachenolide C Reduces the Tumorigenic Properties of KRASCancers · 2024Article
- Review
- Withanolide derivatives: natural compounds with anticancer potential offer low toxicity to fertility and ovarian follicles in mice.Animal reproduction · 2024Article
73 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The purpose of this study is to investigate the efficacy and the mechanism of Hsp90 inhibition of Withaferin A (WA), a steroidal lactone occurring in Withania somnifera, in pancreatic cancer in vitro and in vivo. Withaferin A exhibited potent antiproliferative activity against pancreatic cancer cells in vitro (with IC(50)s of 1.24, 2.93 and 2.78 microM) in pancreatic cancer cell lines Panc-1, MiaPaCa2 and BxPc3, respectively. Annexin V staining showed that WA induced significant apoptosis in Panc-1 cells in a dose-dependent manner. Western blotting demonstrated that WA inhibited Hsp90 chaperone activity to induce degradation of Hsp90 client proteins (Akt, Cdk4 and glucocorticoid receptor), which was reversed by the proteasomal inhibitor, MG132. WA-biotin pull down assay of Hsp90 using Panc-1 cancer cell lysates and purified Hsp90 showed that WA-biotin binds to C-terminus of Hsp90 which was competitively blocked by unlabeled WA. Co-immunoprecipitation exhibited that WA (10 microM) disrupted Hsp90-Cdc37 complexes from 1 to 24h post-treatment, while it neither blocked ATP binding to Hsp90, nor changed Hsp90-P23 association. WA (3, 6mg/kg) inhibited tumor growth in pancreatic Panc-1 xenografts by 30% and 58%, respectively. These data demonstrate that Withaferin A binds Hsp90, inhibits Hsp90 chaperone activity through an ATP-independent mechanism, results in Hsp90 client protein degradation, and exhibits in vivo anticancer activity against pancreatic cancer.
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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.