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. Copyright 2009 Elsevier Inc. All rights reserved.
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. Copyright 2009 Elsevier Inc. All rights reserved.
Authors: Philip R Dash; Judith E Cartwright; Philip N Baker; Alan P Johnstone; Guy St J Whitley Journal: Exp Cell Res Date: 2003-07-15 Impact factor: 3.905
Authors: Husam M Abu-Soud; Dhiman Maitra; Jaeman Byun; Carlos Eduardo A Souza; Jashoman Banerjee; Ghassan M Saed; Michael P Diamond; Peter R Andreana; Subramaniam Pennathur Journal: Free Radic Biol Med Date: 2011-11-10 Impact factor: 7.376
Authors: Richard A Maki; Michael Holzer; Khatereh Motamedchaboki; Ernst Malle; Eliezer Masliah; Gunther Marsche; Wanda F Reynolds Journal: Free Radic Biol Med Date: 2019-06-06 Impact factor: 7.376
Authors: Jimmy Belotte; Nicole M Fletcher; Awoniyi O Awonuga; Mitchell Alexis; Husam M Abu-Soud; Mohammed G Saed; Michael P Diamond; Ghassan M Saed Journal: Reprod Sci Date: 2013-09-27 Impact factor: 3.060
Authors: Dan Cacsire Castillo-Tong; Dietmar Pils; Georg Heinze; Ioana Braicu; Jalid Sehouli; Alexander Reinthaller; Eva Schuster; Andrea Wolf; Rafal Watrowski; Richard A Maki; Robert Zeillinger; Wanda F Reynolds Journal: Tumour Biol Date: 2013-07-27
Authors: Jimmy Belotte; Nicole M Fletcher; Mohammed G Saed; Mohammed S Abusamaan; Gregory Dyson; Michael P Diamond; Ghassan M Saed Journal: PLoS One Date: 2015-08-24 Impact factor: 3.240