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Specific Amino Acid Dependency Regulates Multiple Pathways Controlling Invasiveness and Apoptosis of Prostate Cancer Cells
Author(s) -
Meadows Gary G,
Fu YaMin,
Zhang Hui,
Ding Mingjie
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1011-c
Subject(s) - du145 , protein kinase b , apoptosis , biology , gtp' , pi3k/akt/mtor pathway , mitochondrion , microbiology and biotechnology , chemistry , biochemistry , cancer cell , cancer , enzyme , genetics , lncap
Selective amino acid restriction inhibits invasion and induces apoptosis of PC3 and DU145 prostate cancer cells. In PC3 cells, Tyr/Phe or Met restriction reduces surface alpha5beta1 integrin expression, and Tyr/Phe or Gln restriction reduces the amount of Ras‐GTP. In DU145 cells, Tyr/Phe, Met, or Gln restriction does not affect integrin expression. Tyr/Phe restriction reduces the amount of Rho‐GTP and Rac1‐GTP. Met deprivation reduces Rho‐GTP, and Gln restriction decreases Cdc42‐GTP. These effects contribute to decreased invasiveness. Amino acid restriction differentially modulates the Raf and Akt survival pathways to induce apoptosis. In DU145, Tyr/Phe or Met restriction reduces the activity of Akt and mitochondrial distribution of phosphorylated Raf and AIF, and increases mitochondrial Bak distribution. Tyr/Phe restriction reduces the amount of Bcl‐2 protein and increases Bcl‐XL mitochondrial distribution. Met restriction decreases mitochondrial distribution of Bcl‐XL. In PC3, Met restriction induces apoptosis but this is not associated with alterations in intracellular distribution of Raf, Bcl‐2 family proteins or AIF. All amino acid restrictions inhibited Akt activity. Supported by R01CA101035.