Abstract 39: Specific amino acid restriction affects glucose metabolism and induces oxidative damage of mitochondria in prostate cancer cells

Abstract

Abstract The purpose of this study was to examine how specific amino acid restriction targets mitochondria to induce apoptosis in DU145 and PC3 prostate cancer cells. This study shows that restriction of tyrosine and phenylalanine (Tyr/Phe), glutamine (Gln), and methionine (Met) differentially modulates glucose metabolism, the activity of pyruvate dehydrogenase (PDH) and antioxidant status in the mitochondria of these two cell lines. In DU145 cells, Gln and Met restriction but not Tyr/Phe restriction, increase glucose consumption and decrease lactate production. All the examined restrictions increase mitochondrial PDH activity and reactive oxygen species (ROS). Gln and Met restriction increase mitochondrial activity of glutathione peroxidase (GPx). Tyr/Phe and Met restriction increase mitochondrial activity of manganese superoxide dismutase (SOD) in the first 2 days of the restriction, and the activity returns to basal level on day 4 of restriction. Moreover, all the examined restrictions decrease reduced glutathione (GSH) and cause mitochondrial DNA damage. In PC3 cells, all of the examined restrictions reduce glucose consumption and lactate production; however, they do not alter mitochondrial PDH activity. Gln restriction increases accumulation of ROS and elevates mitochondrial GPx activity. Tyr/Phe restriction increases mitochondrial activity of SOD during the entire restriction period. Although all the restrictions decrease GSH in PC3 cells, they do not cause mitochondrial DNA damage. The data indicate that specific amino acid dependency differentially regulates glucose metabolism, oxidation-reduction reactions of mitochondria, and oxidative damage in mitochondria of these two cell lines. This partially explains how selective amino acid restriction targets mitochondria to induce apoptosis. (The project described was supported by Award Number R01CA101035 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 39.