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Dichloroacetate Induces Apoptosis of Epithelial Ovarian Cancer Cells Through a Mechanism Involving Modulation of Oxidative Stress

Abstract

Epithelial ovarian cancer (EOC) cells are under intrinsic oxidative stress, which alters metabolic activity and reduces apoptosis. Key oxidative stress enzymes, including myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS), are upregulated and colocalized in EOC cells. Oxidative stress is also regulated, in part, by superoxide dismutase (SOD) and hypoxia-inducible factor (HIF) 1a. Dichloroacetate (DCA) converts anaerobic to aerobic metabolism and thus was utilized to determine the effects on apoptosis, iNOS, MPO, extracellular SOD (SOD-3), and HIF-1a, in EOC cells. Protein and messenger RNA (mRNA) levels of iNOS, MPO, SOD-3, and HIF-1a were evaluated by immunoprecipitation/Western blot and real-time reverse transcriptase-polymerase chain reaction (RT-PCR), respectively, utilizing SKOV-3 and MDAH-2774 treated with DCA. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and caspase 3 assays. Dichloroacetate induced apoptosis, reduced MPO, iNOS, and HIF-1a, whereas increased SOD, in both EOC cell lines. In conclusion, reduction of enhanced oxidative stress-induced apoptosis of EOC cells, which may serve as future therapeutic intervention for ovarian cancer.

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Correspondence to Ghassan M. Saed PhD.

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Saed, G.M., Fletcher, N.M., Jiang, Z.L. et al. Dichloroacetate Induces Apoptosis of Epithelial Ovarian Cancer Cells Through a Mechanism Involving Modulation of Oxidative Stress. Reprod. Sci. 18, 1253–1261 (2011) doi:10.1177/1933719111411731

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Keywords

  • epithelial ovarian cancer
  • dichloroacetate
  • real-time RT-PCR
  • apoptosis
  • oxidative stress