Redox state and prostate cancer behavior

Cellular or tissue reduction-oxidation (redox) state is the result of the net balance of molecular reducing and oxidizing equivalents, and can be subdivided into intra-or extracellular redox state (inside or outside the cell), respectively. Under physiological conditions, redox state regulates cell metabolism, survival, and the cell cycle. Prostate cancer is the most common malignancy diagnosed in men and is the second leading cause of cancer deaths in males in the U.S.A. Many studies have documented that prostate cancer cell lines have altered levels of intracellular reactive oxygen species/reactive nitrogen species and/or antioxidant levels in relation to nonmalignant cells. This abnormal intracellular redox state may play an important role in prostate cancer cell cycle progression and cell survival through regulation of redox- modulated transcription factors. Our laboratory recently reported that prostate cancer cells in the cell cultures exhibited an increased glutathione/glutathione disulfide ratio in the media in comparison to immortalized but nonmalignant prostate epithelial cells, suggesting an alteration of extracellular redox state of prostate cancer cells. We also demonstrated that modulation of extracellular redox state by overexpression of extracellular superoxide dismutase resulted in inhibition of prostate cancer cell invasiveness through a mechanism responsive to superoxide radical and/or nitric oxide. We propose that both intra- and extracellular redox states play complementary role(s) in regulation of prostate cancer cell proliferation and/or invasion. This possible relationship between redox states may lead to the development of anti-cancer therapeutics utilizing redox-modulating compounds that are specifically designed to target prostate cancer cells and/or the prostate cancer microenvironment.