Combined application of camptothecin and the guanylate cyclase activator YC-1: Impact on cell death and apoptosis-related proteins in ovarian carcinoma cell lines
- Authors
- Lee, Sun-Joo; Kim, Yun Jeong; Lee, Chung Soo; Bae, Jaeman
- Issue Date
- Oct-2009
- Publisher
- ELSEVIER IRELAND LTD
- Keywords
- Camptothecin; YC-1; Epithelial ovarian cancer cell lines; Apoptotic proteins; Cell death
- Citation
- CHEMICO-BIOLOGICAL INTERACTIONS, v.181, no.2, pp 185 - 192
- Pages
- 8
- Journal Title
- CHEMICO-BIOLOGICAL INTERACTIONS
- Volume
- 181
- Number
- 2
- Start Page
- 185
- End Page
- 192
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/65191
- DOI
- 10.1016/j.cbi.2009.05.013
- ISSN
- 0009-2797
1872-7786
- Abstract
- Camptothecin analogs and guanylate cyclase activator YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole] have been shown to induce apoptosis in cancer cells. However, the combined effect of camptothecin analogs and YC-1 on the viability of epithelial ovarian cancer cells remains uncertain. We assessed the combined effect of YC-1 on the camptothecin toxicity in the human epithelial ovarian carcinoma cell lines OVCAR-3 and SK-OV-3. Camptothecin and YC-1 induced apoptosis in OVCAR-3 and SK-OV-3 cells in a dose- and time-dependent manner. Both compounds induced nuclear damage, decreased Bid and Bcl-2 protein levels, enhanced cytochrome c release, activated caspase-3 and upregulated tumor suppressor p53. Camptothecin decreased Bax protein levels, whereas YC-1 increased Bax levels. YC-1 enhanced the camptothecin-induced changes in the apoptotic protein levels and increased apoptotic effect of camptothecin on ovarian carcinoma cell lines. The results suggested that YC-1 may enhance a camptothecin toxicity against ovarian carcinoma cell lines by increasing activation of the caspase-8 and Bid pathway as well as activation of the mitochondria-mediated apoptotic pathway, leading to cytochrome c release and subsequent caspase-3 activation. Combination of camptothecin analogs and YC-1 may provide a therapeutic benefit against ovarian adenocarcinoma. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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