Tumor necrosis factor-related apoptosis-inducing
ligand (TRAIL) induces apoptosis in various
cancer cells. Hsp90 is known to be involved in cell survival and growth in
tumor cells. Nevertheless, Hsp90 inhibitors exhibit a variable effect on the cytotoxicity of anticancer drugs. Furthermore, the combined effect of Hsp90 inhibitors on TRAIL-induced apoptosis in
epithelial ovarian cancer cells has not been determined. To assess the ability of an inhibitor of Hsp90 inhibitor
radicicol to promote apoptosis, we investigated the effect of
radicicol on TRAIL-induced apoptosis in the human
epithelial ovarian carcinoma cell lines OVCAR-3 and SK-OV-3. TRAIL induced a decrease in Bid, Bcl-2, Bcl-xL, and
survivin protein levels, increase in Bax levels, loss of the mitochondrial transmembrane potential,
cytochrome c release, activation of
caspases (-8, -9, and -3), cleavage of PARP-1 and an increase in the
tumor suppressor p53 levels.
Radicicol enhanced TRAIL-induced apoptosis-related
protein activation, nuclear damage and cell death. These results suggest that
radicicol may potentiate the apoptotic effect of TRAIL on ovarian
carcinoma cell lines by increasing the activation of the caspase-8- and Bid-dependent pathway and the mitochondria-mediated apoptotic pathway, leading to
caspase activation.
Radicicol may confer a benefit in the TRAIL treatment of epithelial ovarian
adenocarcinoma.