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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
- Source :
- European Journal of Pharmacology. 683:54-62
- Publication Year :
- 2012
- Publisher :
- Elsevier BV, 2012.
-
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.
- Subjects :
- Programmed cell death
Indazoles
Licochalcone A
Poly (ADP-Ribose) Polymerase-1
Apoptosis
Carcinoma, Ovarian Epithelial
chemistry.chemical_compound
Chalcones
Cell Line, Tumor
Ovarian carcinoma
Survivin
Humans
Drug Interactions
Neoplasms, Glandular and Epithelial
Caspase
Cell Nucleus
Ovarian Neoplasms
Pharmacology
biology
Carcinoma
Antineoplastic Agents, Phytogenic
Neoplasm Proteins
Cell biology
Enzyme Activation
chemistry
Guanylate Cyclase
Cell culture
Caspases
Proteolysis
Cancer cell
biology.protein
Cancer research
Female
Poly(ADP-ribose) Polymerases
Tumor Suppressor Protein p53
Apoptosis Regulatory Proteins
Signal Transduction
Subjects
Details
- ISSN :
- 00142999
- Volume :
- 683
- Database :
- OpenAIRE
- Journal :
- European Journal of Pharmacology
- Accession number :
- edsair.doi.dedup.....7340fab859647d65e708dc03b831cd2e