Guanylate Cyclase Activator YC-1 Enhances TRAIL-Induced Apoptosis in Human Epithelial Ovarian Carcinoma Cells via Activation of Apoptosis-Related Proteinsopen access
- Authors
- Lee, Chung S.; Kim, Yun J.; Kim, Wonyong; Myung, Soon C.
- Issue Date
- Oct-2011
- Publisher
- WILEY-BLACKWELL
- Citation
- BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY, v.109, no.4, pp 283 - 291
- Pages
- 9
- Journal Title
- BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
- Volume
- 109
- Number
- 4
- Start Page
- 283
- End Page
- 291
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/21226
- DOI
- 10.1111/j.1742-7843.2011.00717.x
- ISSN
- 1742-7835
1742-7843
- Abstract
- To assess the ability of 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1) to promote apoptosis, we investigated the effect of YC-1 on tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in the human epithelial ovarian carcinoma cell lines. In OVCAR-3 and SK-OV-3 cell lines, we examined the stimulatory effect of YC-1 on TRAIL-induced apoptosis by monitoring cell death, nuclear damage, changes in apoptosis-related protein levels, activation of caspases and changes in the mitochondrial transmembrane potential. TRAIL induced a decrease in Bid, Bcl-2 and Bcl-xL protein levels, increase in cleaved Bid and Bax levels, loss of the mitochondrial transmembrane potential, cytochrome c release, activation of caspases (-8, -9 and -3) and an increase in the tumour suppressor p53 levels. YC-1 enhanced TRAIL-induced apoptosis-related protein activation, nuclear damage and cell death. Results from this study suggest that YC-1 may enhance the apoptotic effect of TRAIL on ovarian carcinoma cell lines by increasing the activation of the caspase-8- and Bid-dependent pathways and the mitochondria-mediated apoptotic pathway, leading to caspase activation. YC-1 may confer a benefit in TRAIL treatment of epithelial ovarian adenocarcinoma.
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