Modulation of redox signaling promotes apoptosis in epithelial ovarian cancer cells

Zhongliang Jiang, Nicole M. Fletcher, Rouba Ali-Fehmi, Michael P. Diamond, Husam M. Abu-Soud, Adnan R. Munkarah, Ghassan M. Saed

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Objective: Epithelial ovarian cancer (EOC) cells are known to be resistant to apoptosis through a mechanism that may involve alteration in their redox balance. NADPH oxidase is a major source of intracellular superoxide, which is converted to the less toxic product by superoxide dismutase (SOD). Superoxide contributes to hypoxia inducible factor (HIF)-1α stabilization. We sought to determine the effects of inhibiting the generation of intracellular reactive oxygen species (ROS) on apoptosis of EOC cells. Methods: Diphenyleneiodonium (DPI), an irreversible ROS inhibitor, was used to inhibit the generation of ROS in EOC cell lines, SKOV-3 and MDAH-2774, followed by assessment of apoptosis, NADPH oxidase, SOD3 and HIF-1α expression. A combination of immunohistochemistry, immunoprecipitation/western blot, and real-time RT-PCR were utilized to evaluate the expression of these enzymes in EOC cells as well as normal ovarian tissue and ovarian cancer tissue specimens. Results: DPI treatment significantly induced apoptosis in both EOC cell lines as evident by increased caspase-3 activity and TUNEL assay. Additionally, both EOC cell lines were found to express NADPH oxidase, HIF-1α, and SOD3, which were highly sensitive to DPI treatment. DPI treatment resulted in reduced NADPH oxidase, SOD3 and HIF-1α levels. Furthermore, ovarian cancer tissues were found to manifest higher NADPH oxidase levels as compared to normal ovarian tissues. Conclusions: These data suggest that lowering oxidative stress, possibly through the inhibition of NADPH oxidase, induces apoptosis in ovarian cancer cells and may serve as a potential target for cancer therapy.

Original languageEnglish (US)
Pages (from-to)418-423
Number of pages6
JournalGynecologic Oncology
Volume122
Issue number2
DOIs
StatePublished - Aug 2011

Keywords

  • Diphenyleneiodonium
  • Epithelial ovarian cancer
  • Hypoxia inducible factor-1 alpha
  • NADPH oxidase
  • Oxidative stress
  • Superoxide dismutase

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

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  • Cite this

    Jiang, Z., Fletcher, N. M., Ali-Fehmi, R., Diamond, M. P., Abu-Soud, H. M., Munkarah, A. R., & Saed, G. M. (2011). Modulation of redox signaling promotes apoptosis in epithelial ovarian cancer cells. Gynecologic Oncology, 122(2), 418-423. https://doi.org/10.1016/j.ygyno.2011.04.051