title: Guanylate cyclase activator YC-1 enhances TRAIL-induced apoptosis in human epithelial ovarian carcinoma cells via activation of apoptosis-related proteins.
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.
authors.affiliation: Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, South Korea. leecs@cau.ac.kr
authors.forename: Chung S
authors.initials: CS
authors.lastname: Lee
authors.forename: Yun J
authors.initials: YJ
authors.lastname: Kim
authors.forename: Wonyong
authors.initials: W
authors.lastname: Kim
authors.forename: Soon C
authors.initials: SC
authors.lastname: Myung
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D020536:Enzyme Activators / Q000494:pharmacology*; D005260:Female; D006162:Guanylate Cyclase / Q000378:metabolism*; D006801:Humans; D007191:Indazoles / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*
chemical_list: D014408:Biomarkers, Tumor; D020536:Enzyme Activators; D007191:Indazoles; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C076744:cytoplasmic linker protein 170; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; D053181:Caspase 8; D006162:Guanylate Cyclase