Dichloroacetate induces apoptosis of epithelial ovarian cancer cells through a mechanism involving modulation of oxidative stress

Ghassan M. Saed, Nicole M. Fletcher, Zhong L. Jiang, Husam M. Abu-Soud, Michael P. Diamond

Research output: Contribution to journalArticle

34 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1253-1261
Number of pages9
JournalReproductive Sciences
Volume18
Issue number12
DOIs
StatePublished - Dec 1 2011
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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