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学科主题: 基础医学
题名:
Cell Death of Prostate Cancer Cells by Specific Amino Acid Restriction Depends on Alterations of Glucose Metabolism
作者: Fu, Ya-Min1; Lin, Huimin1; Fang, Weigang2; Meadows, Gary G.1
刊名: JOURNAL OF CELLULAR PHYSIOLOGY
发表日期: 2010-08-01
DOI: 10.1002/jcp.22148
卷: 224, 期:2, 页:491-500
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell Biology ; Physiology
研究领域[WOS]: Cell Biology ; Physiology
关键词[WOS]: GLYCOGEN-SYNTHASE KINASE-3-BETA ; CHEMOTHERAPY-INDUCED APOPTOSIS ; INTESTINAL EPITHELIAL-CELLS ; FOCAL ADHESION KINASE ; P53-DEPENDENT APOPTOSIS ; AKT ; PATHWAY ; ACTIVATION ; PROTEIN ; BAX
英文摘要:

Selective amino acid restriction targets mitochondria resulting in DU145 and PC3 prostate cancer cell death. This study shows that restriction of tyrosine and phenylalanine (Tyr/Phe), glutamine (Gin), or methionine (Met) differentially modulates glucose metabolism, glycogen synthase kinase 3 beta (GSK3 beta), p53, and pyruvate dehydrogenase (PDH) in these two cell lines. In DU145 cells, Gin and Met restriction increase glucose consumption, but Tyr/Phe restriction does not. Addition of glucose to culture media diminishes cell death induced by Tyr/Phe-restriction. Addition of pyruvate reduces cell death due to Tyr/Phe and Gln restriction. Tyr/Phe, Gln and Met restriction increase phosphorylation of GSK3 beta-Ser(9), phosphorylation of p53-Ser(15) and reduce the mitochondrial localization of PDH. Addition of glucose or pyruvate to cultures significantly reverses the alterations in GSK3 beta, p53 and PDH induced by amino acid restriction. In p53-null PC3 cells, Tyr/Phe, Gln and Met restriction decreases glucose consumption, reduces phosphorylation of Akt-Ser(473), and increases phosphorylation of GSK3 beta-Ser(9). Addition of pyruvate or glucose reduces death of Met-restricted cells. Addition of glucose increases phosphorylation of Akt-Ser473 in amino acid-restricted cells reduces phosphorylation of GSK3 beta-Ser(9) in Tyr/Phe and Gin restricted cells and increases phosphorylation of GSK3 beta-Ser(9) in Met restricted cells. Addition of pyruvate reduces phosphorylation of GSK3 beta-Ser(9) in all amino acid-restricted cells. In summary, cell death induced by specific amino acid restriction is dependent on or closely related to the modulation of glucose metabolism. GSK3 beta (DU145 and PC3) and p53 (DU145) are crucial switches connecting metabolism and these signaling molecules to cell survival during amino acid restriction. J. Cell. Physiol. 224: 491-500, 2010. (C) 2010 Wiley-Liss, Inc.

语种: 英语
所属项目编号: R01CA101035
项目资助者: National Institutes of Health, National Cancer Institute
WOS记录号: WOS:000279418600025
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67308
Appears in Collections:基础医学院_病理学系_期刊论文

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作者单位: 1.Washington State Univ, Dept Pharmaceut Sci, Coll Pharm, Pullman, WA 99164 USA
2.Peking Univ, Hlth Sci Ctr, Dept Pathol, Beijing 100871, Peoples R China

Recommended Citation:
Fu, Ya-Min,Lin, Huimin,Fang, Weigang,et al. Cell Death of Prostate Cancer Cells by Specific Amino Acid Restriction Depends on Alterations of Glucose Metabolism[J]. JOURNAL OF CELLULAR PHYSIOLOGY,2010,224(2):491-500.
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