Myeloperoxidase serves as a redox switch that regulates apoptosis in epithelial ovarian cancer

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

Research output: Contribution to journalArticle

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Abstract

Objectives: Resistance to apoptosis is a key feature of cancer cells and is believed to be regulated by nitrosonium ion (NO+)-induced S-nitrosylation of key enzymes. Nitric oxide (NO), produced by inducible nitric oxide synthase (iNOS), is utilized by MPO to generated NO+. We sought to investigate the expression of myeloperoxidase (MPO) and iNOS in epithelial ovarian cancer (EOC) and determine their effect on S-nitrosylation of caspase-3 and its activity as well as apoptosis. Methods: MPO and iNOS expression were determined using immunofluorescence in SKOV-3 and MDAH-2774 and EOC tissue sections. S-nitrosylation of caspase-3 and its activity, levels of MPO and iNOS, as well as apoptosis, were evaluated in the EOC cells before and after silencing MPO or iNOS genes with specific siRNA probes utilizing real-time RT-PCR, ELISA, and TUNEL assays. Results: MPO and iNOS are expressed in EOC cell lines and in over 60% of invasive EOC cases with no expression in normal ovarian epithelium. Indeed, silencing of MPO or iNOS gene expression resulted in decreased S-nitrosylation of caspase-3, increased caspase-3 activity, and increased apoptosis but with a more significant effect when silencing MPO. Conclusion: MPO and iNOS are colocalized to the same cells in EOC but not in the normal ovarian epithelium. Silencing of either MPO or iNOS significantly induced apoptosis, highlighting their role as a redox switch that regulates apoptosis in EOC. Understanding the mechanisms by which MPO functions as a redox switch in regulating apoptosis in EOC may lead to future diagnostic tools and therapeutic interventions.

Original languageEnglish (US)
Pages (from-to)276-281
Number of pages6
JournalGynecologic Oncology
Volume116
Issue number2
DOIs
StatePublished - Feb 1 2010

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Peroxidase
Oxidation-Reduction
Nitric Oxide Synthase Type II
Apoptosis
Caspase 3
Nitric Oxide
Ovarian epithelial cancer
Epithelium
In Situ Nick-End Labeling
Small Interfering RNA
Fluorescent Antibody Technique
Real-Time Polymerase Chain Reaction
Enzyme-Linked Immunosorbent Assay
Gene Expression
Cell Line
Enzymes

Keywords

  • Apoptosis
  • Caspase-3
  • Epithelial ovarian cancer
  • Inducible nitric oxide synthase
  • Myeloperoxidase
  • S-nitrosylation

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

Saed, G. M., Ali-Fehmi, R., Jiang, Z. L., Fletcher, N. M., Diamond, M. P., Abu-Soud, H. M., & Munkarah, A. R. (2010). Myeloperoxidase serves as a redox switch that regulates apoptosis in epithelial ovarian cancer. Gynecologic Oncology, 116(2), 276-281. https://doi.org/10.1016/j.ygyno.2009.11.004

Myeloperoxidase serves as a redox switch that regulates apoptosis in epithelial ovarian cancer. / Saed, Ghassan M.; Ali-Fehmi, Rouba; Jiang, Zhong L.; Fletcher, Nicole M.; Diamond, Michael Peter; Abu-Soud, Husam M.; Munkarah, Adnan R.

In: Gynecologic Oncology, Vol. 116, No. 2, 01.02.2010, p. 276-281.

Research output: Contribution to journalArticle

Saed, GM, Ali-Fehmi, R, Jiang, ZL, Fletcher, NM, Diamond, MP, Abu-Soud, HM & Munkarah, AR 2010, 'Myeloperoxidase serves as a redox switch that regulates apoptosis in epithelial ovarian cancer', Gynecologic Oncology, vol. 116, no. 2, pp. 276-281. https://doi.org/10.1016/j.ygyno.2009.11.004
Saed, Ghassan M. ; Ali-Fehmi, Rouba ; Jiang, Zhong L. ; Fletcher, Nicole M. ; Diamond, Michael Peter ; Abu-Soud, Husam M. ; Munkarah, Adnan R. / Myeloperoxidase serves as a redox switch that regulates apoptosis in epithelial ovarian cancer. In: Gynecologic Oncology. 2010 ; Vol. 116, No. 2. pp. 276-281.
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abstract = "Objectives: Resistance to apoptosis is a key feature of cancer cells and is believed to be regulated by nitrosonium ion (NO+)-induced S-nitrosylation of key enzymes. Nitric oxide (NO), produced by inducible nitric oxide synthase (iNOS), is utilized by MPO to generated NO+. We sought to investigate the expression of myeloperoxidase (MPO) and iNOS in epithelial ovarian cancer (EOC) and determine their effect on S-nitrosylation of caspase-3 and its activity as well as apoptosis. Methods: MPO and iNOS expression were determined using immunofluorescence in SKOV-3 and MDAH-2774 and EOC tissue sections. S-nitrosylation of caspase-3 and its activity, levels of MPO and iNOS, as well as apoptosis, were evaluated in the EOC cells before and after silencing MPO or iNOS genes with specific siRNA probes utilizing real-time RT-PCR, ELISA, and TUNEL assays. Results: MPO and iNOS are expressed in EOC cell lines and in over 60{\%} of invasive EOC cases with no expression in normal ovarian epithelium. Indeed, silencing of MPO or iNOS gene expression resulted in decreased S-nitrosylation of caspase-3, increased caspase-3 activity, and increased apoptosis but with a more significant effect when silencing MPO. Conclusion: MPO and iNOS are colocalized to the same cells in EOC but not in the normal ovarian epithelium. Silencing of either MPO or iNOS significantly induced apoptosis, highlighting their role as a redox switch that regulates apoptosis in EOC. Understanding the mechanisms by which MPO functions as a redox switch in regulating apoptosis in EOC may lead to future diagnostic tools and therapeutic interventions.",
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AU - Saed, Ghassan M.

AU - Ali-Fehmi, Rouba

AU - Jiang, Zhong L.

AU - Fletcher, Nicole M.

AU - Diamond, Michael Peter

AU - Abu-Soud, Husam M.

AU - Munkarah, Adnan R.

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