Differential effects of specific amino acid restriction on glucose metabolism, reduction/oxidation status and mitochondrial damage in DU145 and PC3 prostate cancer cells

Liu,Xiaoyi; Fu,Ya-Min; Meadows,Gary  G.

doi:10.3892/ol.2011.237

March-April 2011 Volume 2 Issue 2

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March-April 2011 Volume 2 Issue 2

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Article

Differential effects of specific amino acid restriction on glucose metabolism, reduction/oxidation status and mitochondrial damage in DU145 and PC3 prostate cancer cells

Authors:
- Xiaoyi Liu
- Ya-Min Fu
- Gary G. Meadows
View Affiliations / Copyright

Affiliations: Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman, WA 99164-6534, USA
Pages: 349-355
|
Published online on: January 18, 2011

https://doi.org/10.3892/ol.2011.237
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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.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Differential effects of specific amino acid restriction on glucose metabolism, reduction/oxidation status and mitochondrial damage in DU145 and PC3 prostate cancer cells

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