Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, South Korea.
Eur J Pharmacol. 2010 Dec 15;649(1-3):354-61. doi: 10.1016/j.ejphar.2010.09.047. Epub 2010 Sep 22.
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.
甘草衍生化合物甘草酸和 18β-甘草次酸已被证明可诱导多种癌细胞凋亡。然而，这些甘草化合物对上皮性卵巢癌细胞组蛋白去乙酰化酶抑制剂诱导的凋亡的影响尚未确定。我们评估了 18β-甘草次酸对人类上皮性癌细胞系 OVCAR-3 和 SK-OV-3 中曲古抑菌素 A 诱导的凋亡的影响。曲古抑菌素 A 诱导核损伤，降低 Bid 和 Bcl-2 蛋白水平，增加 Bax 水平，诱导细胞色素 c 释放，激活 caspase-8、-9 和 -3，并增加肿瘤抑制因子 p53 水平。18β-甘草次酸增强了曲古抑菌素 A 诱导的与凋亡相关的蛋白激活和细胞死亡。与 18β-甘草次酸不同，高达 25μM 的前体化合物甘草酸苷不会诱导细胞死亡，也不会影响曲古抑菌素 A 诱导的凋亡。结果表明，18β-甘草次酸可能通过增加 caspase-8 依赖性途径以及线粒体介导的细胞死亡途径的激活，从而激活 caspase，增强曲古抑菌素 A 对卵巢癌细胞系的凋亡作用。18β-甘草次酸可能增强曲古抑菌素 A 对上皮性卵巢腺癌的治疗效果。
