Abstract 3792: Specific amino acid restriction differentially induces autophagy in DU145 and PC3 human prostate cancer cell lines

Abstract

Abstract We previously found that selective amino acid restriction differentially induces death of DU145 and PC3 human prostate cancer cells. Herein we examined the hypothesis that this differential cell death was associated with induction of autophagy. By detecting the immunofluorescence of microtubule-associated protein 1A/1B light chain 3 (LC3) by confocal microscopy, this study shows that selective amino acid restriction also differentially induces autophagy in DU145 and PC3 human prostate cancer cell lines. In DU145 cells, restriction of tyrosine and phenylalanine (Tyr/Phe), glutamine (Gln), and methionine (Met) induces autophagy. Addition of pyruvate significantly increases Tyr/Phe restriction-induced autophagy and significantly reduces Met and Gln restriction-induced autophagy. All of the amino acid restrictions induce cell death in DU145 cells. Pyruvate, a major metabolite of glucose metabolism, significantly reduces Tyr/Phe and Gln restriction-mediated cell death, but not Met restriction-medicated cell death. Tyr/Phe and Gln restriction induces autophagy in PC3 cells. Addition of pyruvate does not alter Tyr/Phe restriction-induced autophagy but significantly increases Met and Gln restriction-induced autophagy. Only Met restriction induces cell death in this cell line, and pyruvate addition reverses this effect. In summary, the present study indicates 1) cell line specific differences between DU145 and PC3 cells in the induction of autophagy by specific amino acid restriction, 2) lack of association between induction of autophagy and cell death, and 3) differential effects of pyruvate on autophagy and cell death. (This study was supported by grant R01CA101035 from the National Cancer Institute). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3792. doi:10.1158/1538-7445.AM2011-3792