18β-Glycyrrhetinic acid potentiates Hsp90 inhibition-induced apoptosis in human epithelial ovarian carcinoma cells via activation of death receptor and mitochondrial pathway

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• 作者：Jae Chon Yang (1)
  Soon Chul Myung (2)
  Wonyong Kim (3)
  Chung Soo Lee (1) leecs@cau.ac.kr
• 关键词：Hsp90 inhibition – 18β ; glycyrrhetinic acid – Epithelial ovarian adenocarcinoma cell lines – Apoptosis ; related proteins – Promoting effect
• 刊名：Molecular and Cellular Biochemistry
• 出版年：2012
• 出版时间：November 2012
• 年：2012
• 卷：370
• 期：1-2
• 页码：209-219
• 全文大小：578.5 KB
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• 作者单位：1. Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, 156-756 South Korea2. Department of Urology, Chung-Ang University Hospital, Seoul, 156-755 South Korea3. Department of Microbiology, College of Medicine, Chung-Ang University, Seoul, 156-756 South Korea
• ISSN：1573-4919

文摘

The Hsp90 inhibition has been shown to induce apoptosis in various cancer cells. The licorice compounds may enhance the anti-cancer drug effect. However, effect of the licorice compounds on the Hsp90 inhibition-induced apoptosis in ovarian cancer cells has not been studied. To assess the ability of 18β-glycyrrhetinic acid to promote apoptosis, we examined whether 18β-glycyrrhetinic acid potentiated the Hsp90 inhibitor-induced apoptosis in the human epithelial ovarian carcinoma cell lines OVCAR-3 and SK-OV-3. Radicicol and geldanamycin induced a decrease in Bid, Bcl-2, Bcl-xL and survivin protein levels, an increase in Bax levels, the mitochondrial transmembrane potential loss, cytochrome c release, activation of caspases (-8, -9, and -3), cleavage of PARP-1, and an increase in the tumor suppressor p53 levels. 18β-Glycyrrhetinic acid enhanced Hsp90 inhibitor-induced apoptosis-related protein activation, nuclear damage, and cell death. The results suggest that 18β-glycyrrhetinic acid may potentiate the Hsp90 inhibition-induced apoptosis in ovarian carcinoma cell lines via the activation of the caspase-8- and Bid-dependent pathways and the mitochondria-mediated cell death pathway, leading to activation of caspases. Combination of Hsp90 inhibitors and 18β-glycyrrhetinic acid may confer a benefit in the treatment of epithelial ovarian adenocarcinoma.