Gedunin inactivates the co-chaperone p23 protein causing cancer cell death by apoptosis

Chaitanya A. Patwardhan, Abdul Fauq, Laura B. Peterson, Charles Miller, Brian S.J. Blagg, Ahmed Chadli

Research output: Contribution to journalArticle

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Abstract

Background: The Hsp90 chaperoning machine is an exciting therapeutic target for cancer treatment. Results: We report that the natural product gedunin inactivates the Hsp90 co-chaperone p23 in vitro and in vivo. The lethal effect of gedunin-p23 complex on cancer cells is amplified by caspase-7-mediated cleavage of the co-chaperone, leading to apoptotic cell death. Conclusions: Gelduin binds directly to p23 leading to inactivation of the Hsp90 machine and selective destabilization of steroid receptors. Significance: Gedunin is a promising compound to develop anti-cancer therapeutics.

Original languageEnglish (US)
Pages (from-to)7313-7325
Number of pages13
JournalJournal of Biological Chemistry
Volume288
Issue number10
DOIs
StatePublished - Mar 8 2013

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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