title: Guanylate cyclase activator YC-1 potentiates apoptotic effect of licochalcone A on human epithelial ovarian carcinoma cells via activation of death receptor and mitochondrial pathways.
abstract: Natural phenol licorice compounds have been shown to induce apoptosis in cancer cells. 3-(5'-Hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1) may enhance the sensitivity of cancer cells to anticancer drugs. However, the combined effect of licochalcone A and YC-1 on cell death in ovarian cancer cells has not been studied. We assessed the combined effect of licochalcone A and YC-1 on apoptosis in human epithelial ovarian carcinoma cell lines in relation to the cell death process. In the OVCAR-3 and SK-OV-3 cell lines, licochalocone A induced a decrease in Bid, Bcl-2, Bcl-xL and survivin protein levels; an increase in Bax levels; loss of the mitochondrial transmembrane potential; cytochrome c release; activation of caspases (-8, -9 and -3); cleavage of PARP-1; and an increase in the tumor suppressor p53 levels. YC-1 enhanced licochalcone A-induced apoptosis-related protein activation, nuclear damage and cell death. These results suggest that YC-1 may potentiate the apoptotic effect of licochalcone A on ovarian carcinoma cell lines by increasing the activation of the caspase-8- and Bid-dependent pathway and the mitochondria-mediated apoptotic pathway, leading to caspase activation. The combination of licochalcone A and YC-1 may confer a benefit in the treatment of human epithelial ovarian adenocarcinoma.
authors.affiliation: Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, South Korea. leecs@cau.ac.kr
authors.forename: Chung Soo
authors.initials: CS
authors.lastname: Lee
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Kwak
authors.forename: Yun Jeong
authors.initials: YJ
authors.lastname: Kim
authors.forename: Seon Ae
authors.initials: SA
authors.lastname: Lee
authors.forename: Eon Sob
authors.initials: ES
authors.lastname: Park
authors.forename: Soon Chul
authors.initials: SC
authors.lastname: Myung
authors.forename: Wonyong
authors.initials: W
authors.lastname: Kim
authors.forename: Min Sung
authors.initials: MS
authors.lastname: Lee
authors.forename: Jeong Jae
authors.initials: JJ
authors.lastname: Lee
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000077216:Carcinoma, Ovarian Epithelial; D020169:Caspases / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects; D047188:Chalcones / Q000494:pharmacology*; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects*; D005260:Female; D006162:Guanylate Cyclase / Q000737:chemistry*; D006801:Humans; D007191:Indazoles / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000819:agonists; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D059748:Proteolysis / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D047188:Chalcones; D007191:Indazoles; D009363:Neoplasm Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases; D006162:Guanylate Cyclase; C070840:licochalcone A