The Hsp90 inhibitor 17-(allylamino)-17-demethoxygeldanamycin increases cisplatin antitumor activity by inducing p53-mediated apoptosis in head and neck cancer.

ABSTRACT: The tumor suppressor p53 is often inactivated in head and neck cancer (HNC) through TP53 mutations or overexpression of mouse double minute 2 or mouse double minute X. Restoration of p53 function by counteracting these p53 repressors is a promising strategy for cancer treatment. The present study assessed the ability of a heat shock protein 90 (Hsp90) inhibitor, 17-(Allylamino)-17-demethoxygeldanamycin (17AAG), to induce apoptosis in HNC by restoring p53 function. The effect of 17AAG, alone or in combination with Nutlin-3a or cisplatin, was assessed in HNC cells using growth and apoptosis, immunoblotting, quantitative reverse transcription-polymerase chain reaction, and preclinical tumor xenograft models. 17AAG activated and stabilized p53 in HNC cells bearing wild-type TP53 by disrupting

SUBMITTER: Roh JL 

PROVIDER: S-EPMC3877559 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature