17-Allylamino-17-demethoxygeldanamycin and Herbimycin A Induce Cell Death by Modulating β-Catenin and PI3K/AKT Signaling in FRO Anaplastic Thyroid Carcinoma Cells

The aim of the present study was to evaluate the effect of heat-shock protein 90 (HSP90) inhibitors, 17-allylamino-17-demethoxygeldanamycin (17-AAG) and herbimycin A (HMA) on survival of anaplastic thyroid carcinoma (ATC) cells.Antitumor activities of 17-AAG and HMA were investigated in FRO ATC cells.In FRO ATC cells, 17-AAG and HMA caused cell death with concomitant changes in the expression of HSP90 client proteins, increased β-catenin protein levels, and inhibited PI3K/AKT signaling. The inactivation of β-catenin by β-catenin siRNA transfection and the activation of PI3K/AKT signaling by p110α plasmid transfection abrogated cell death caused by 17-AAG and HMA.17-AAG and HMA have cytotoxic activities accompanied by regulation of HSP90 client proteins, and cytotoxicity is associated with overexpression of β-catenin and suppression of PI3K/AKT signaling in FRO ATC cells.