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

Eur J Pharmacol. 2012 May 15;683(1-3):54-62. doi: 10.1016/j.ejphar.2012.03.024. Epub 2012 Mar 23.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Carcinoma / drug therapy
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Carcinoma, Ovarian Epithelial
  • Caspases / chemistry
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cell Nucleus / drug effects
  • Chalcones / pharmacology*
  • Drug Interactions
  • Enzyme Activation / drug effects*
  • Female
  • Guanylate Cyclase / chemistry*
  • Humans
  • Indazoles / pharmacology*
  • Neoplasm Proteins / agonists
  • Neoplasms, Glandular and Epithelial / drug therapy*
  • Neoplasms, Glandular and Epithelial / metabolism
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / metabolism
  • Proteolysis / drug effects
  • Signal Transduction / drug effects
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Apoptosis Regulatory Proteins
  • Chalcones
  • Indazoles
  • Neoplasm Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • Caspases
  • Guanylate Cyclase
  • licochalcone A