Metabolic Stress Induced by Arginine Deprivation Induces Autophagy Cell Death in Prostate Cancer
Annual rept. 1 Aug 2008-31 Jul 2009
CALIFORNIA UNIV DAVIS
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The primary purpose of this research grant is to provide the necessary preclinical data demonstrating that prostate cancer cells are auxotrophic for arginine and therefore targeting arginine metabolism is a novel therapeutic approach. The primary methodology involves cell culture with the characterization of the arginine requirements for prostate cancer cell growth and then determination of the effect of arginine depletion on cell growth and cell death. Furthermore, we have investigated the mechanism of cell death and observed that arginine deprivation in those cells auxotrophic for this semi-essential amino acid induces autophagy as a precursor to programmed cell death. Major findings to date include the observation that the majority of prostate cancer cell lines lack arginine-succinate synthetase ASS, the critical enzyme in arginine biosynthesis. Furthermore, arginine deprivation in those cell lines lacking ASS induces autophagy as a precursor to non-apoptotic cell death. Inhibition of autophagy appears to stimulate the induction of cell death.
- Medicine and Medical Research