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Role of Mitochondria in Prostate Cancer
Annual summary rept. 15 Nov 2004-14 Nov 2005
HAMILTON HEALTH SCIENCES CORP (ONTARIO)
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Most malignant cells are highly glycolytic and produce high levels of reactive oxygen species ROS compared to normal cells. Mitochondrial glycerophosphate dehydrogenase mGPDH participates in delivering reducing equivalents from this molecule into the electron transport chain, thus sustaining of glycolysis. Here we investigate the role of mGPDH in maintaining an increased rate of glycolysis and evaluate glycerophosphate-dependent ROS generation in prostate cancer cell lines LNCaP, DU145, PC3, and CL1. Immunoblot, Real Time RTPCR, polarographic, and spectrophotometric analysis revealed that mGPDH abundance and activity was significantly elevated in prostate cancer cell lines when compared to normal prostate epithelial cell line PNT1A. Furthermore, both the glycolytic capacity and glycerophosphate-dependent ROS production was increased 1.68-4.44 fold and 5-7 fold, respectively in prostate cancer cell lines when compared to PNT1A cells. Overall, these data demonstrate that mGPDH is involved in maintaining a high rate of glycolysis and is an important site of electron leakage leading to ROS production in prostate cancer cells.
APPROVED FOR PUBLIC RELEASE