Dual effects of glutathione-S-transferase π on As2O 3 action in prostate cancer cells: Enhancement of growth inhibition and inhibition of apoptosis

Min Lu, Lijuan Xia, David Luo, Samuel Waxman, Yongkui Jing

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

To determine the effects of glutathione-S-transferase π (GSTπ) on the actions of As2O3, As2O3-induced growth inhibition and apoptosis was studied in three prostate cancer cell lines: DU-145, PC-3 and LNCaP cells. As2O3 inhibited cell proliferation of DU-145 and PC-3 cells (both cells express GSTπ), but not of LNCaP cells (which lack GSTπ expression) at concentrations below 1 μM. LNCaP cells stably transfected and expressed GSTπ (LNCaP/ GSTπ) became sensitive to As2O3 growth inhibition. As2O 3 arrested cell growth of DU-145, PC-3 and LNCaP/GSTπ cells in the G2/M phase of the cell cycle at low concentrations (<2 μM), but did not induce apoptosis. At higher concentrations (10-20 μM), As2O 3 induced apoptosis in LNCaP cells, but not in DU-145 or PC-3 cells. The apoptosis induction due to As2O3 treatment of LNCaP cell correlated with the activation of JNK and p38 and induction of p53 protein. LNCaP/ GSTπ cells became insensitive to As2O3-induced apoptosis with reduced JNK activition. These data indicate that GSTπ increases growth inhibition due to As2O3 treatment and prevents As2O3-induced apoptosis in prostate cancer cells. Therefore, it appears that As2O3 inhibits cell growth and induces apoptosis through different mechanisms.

Original languageEnglish
Pages (from-to)3945-3952
Number of pages8
JournalOncogene
Volume23
Issue number22
DOIs
StatePublished - 13 May 2004

Keywords

  • Arsenic trioxide
  • Glutathione-S-transferase π
  • Prostate cancer

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