18 beta-Glycyrrhetinic acid potentiates Hsp90 inhibition-induced apoptosis in human epithelial ovarian carcinoma cells via activation of death receptor and mitochondrial pathway
- Authors
- Yang, Jae Chon; Myung, Soon Chul; Kim, Wonyong; Lee, Chung Soo
- Issue Date
- Nov-2012
- Publisher
- SPRINGER
- Keywords
- Hsp90 inhibition; 18 beta-glycyrrhetinic acid; Epithelial ovarian adenocarcinoma cell lines; Apoptosis-related proteins; Promoting effect
- Citation
- MOLECULAR AND CELLULAR BIOCHEMISTRY, v.370, no.1-2, pp 209 - 219
- Pages
- 11
- Journal Title
- MOLECULAR AND CELLULAR BIOCHEMISTRY
- Volume
- 370
- Number
- 1-2
- Start Page
- 209
- End Page
- 219
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/20034
- DOI
- 10.1007/s11010-012-1412-x
- ISSN
- 0300-8177
1573-4919
- Abstract
- 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 18 beta-glycyrrhetinic acid to promote apoptosis, we examined whether 18 beta-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. 18 beta-Glycyrrhetinic acid enhanced Hsp90 inhibitor-induced apoptosis-related protein activation, nuclear damage, and cell death. The results suggest that 18 beta-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 18 beta-glycyrrhetinic acid may confer a benefit in the treatment of epithelial ovarian adenocarcinoma.
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