title: Differential effects of specific amino acid restriction on glucose metabolism, reduction/oxidation status and mitochondrial damage in DU145 and PC3 prostate cancer cells.
abstract: Selective amino acid restriction targets mitochondria to induce apoptosis of DU145 and PC3 prostate cancer cells. Biochemical assays and flow cytometry were uitilized to analyze the glucose consumption, lactate production, pyruvate dehydrogenase (PDH), nicotinamide adenine dinucleotide (NAD)/NADH and nicotinamide adenine dinucleotide phosphate (NADP)/NADPH ratios, mitochondrial glutathione peroxidase (GPx), manganese superoxide dismutase (SOD), glutathione, reactive oxygen species (ROS) and DNA damage in DU145 and PC prostate cancer cells cultured under various amino acid deprived conditions. Restriction of tyrosine and phenylalanine (Tyr/Phe), glutamine (Gln) or methionine (Met) differentially modulated glucose metabolism and PDH and antioxidant enzyme activity in the mitochondria of the two prostate cancer cell lines. In DU145 cells, Gln and Met restriction increased glucose consumption and decreased lactate production, but Tyr/Phe restriction did not. The examined restrictions increased mitochondrial PDH activity and accumulation of ROS. Gln and Met restriction increased GPx activity. Tyr/Phe and Met restriction increased SOD during the first 2 days of the restriction, and the activity returned to the basal level on day 4. All amino acid restrictions decreased reduced glutathione (GSH) and induced mitochondrial DNA damage. In PC3 cells, all amino acid restrictions reduced glucose consumption and lactate production. Gln restriction increased ROS and elevated GPx activity. Tyr/Phe restriction increased SOD activity. The amino acid restriction decreased GSH, but did not cause mitochondrial DNA damage. Specific amino acid dependency differentially regulates glucose metabolism, oxidation-reduction reactions of mitochondria and mitochondrial damage in DU145 and PC3 prostate cancer cell lines.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman, WA 99164-6534, USA.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Liu
authors.forename: Ya-Min
authors.initials: YM
authors.lastname: Fu
authors.forename: Gary G
authors.initials: GG
authors.lastname: Meadows