18β-Glycyrrhetinic acid potentiates apoptotic effect of trichostatin A on human epithelial ovarian carcinoma cell lines.

The licorice-derived compounds glycyrrhizin and 18β-glycyrrhetinic acid have been shown to induce apoptosis in various cancer cells. However, the effect of these licorice compounds on the apoptotic effect of histone deacetylase inhibitors in epithelial ovarian carcinoma cells has not been determined. We assessed the effect of 18β-glycyrrhetinic acid on trichostatin A-induced apoptosis in the human epithelial carcinoma cell lines OVCAR-3 and SK-OV-3. Trichostatin A induced nuclear damage, decreased Bid and Bcl-2 protein levels, increased in Bax levels, induced cytochrome c release, activated caspase-8, -9 and -3, and increased tumor suppressor p53 levels. 18β-Glycyrrhetinic acid potentiated the trichostatin A-induced apoptosis-related protein activation and cell death. Unlike 18β-glycyrrhetinic acid, up to 25 μM of the pro-compound glycyrrhizin did not induce cell death and did not affect trichostatin A-induced apoptosis. The results suggest that 18β-glycyrrhetinic acid may potentiate the apoptotic effects of trichostatin A against ovarian carcinoma cell lines by increasing the activation of the caspase-8-dependent pathway as well as the activation of the mitochondria-mediated cell death pathway, leading to activation of caspases. 18β-Glycyrrhetinic acid may enhance the therapeutic effect of trichostatin A against epithelial ovarian adenocarcinoma.