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

62 Citations (Scopus)

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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Cell death
Cell Death
Apoptosis
Caspase 7
Neoplasms
Oncology
Steroid Receptors
Biological Products
Cells
Therapeutics
protein p23
gedunin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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Gedunin inactivates the co-chaperone p23 protein causing cancer cell death by apoptosis. / Patwardhan, Chaitanya A.; Fauq, Abdul; Peterson, Laura B.; Miller, Charles; Blagg, Brian S.J.; Chadli, Ahmed.

In: Journal of Biological Chemistry, Vol. 288, No. 10, 08.03.2013, p. 7313-7325.

Research output: Contribution to journalArticle

Patwardhan, Chaitanya A. ; Fauq, Abdul ; Peterson, Laura B. ; Miller, Charles ; Blagg, Brian S.J. ; Chadli, Ahmed. / Gedunin inactivates the co-chaperone p23 protein causing cancer cell death by apoptosis. In: Journal of Biological Chemistry. 2013 ; Vol. 288, No. 10. pp. 7313-7325.
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