Journal
ONCOGENE
Volume 23, Issue 22, Pages 3945-3952Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1207500
Keywords
arsenic trioxide; prostate cancer; glutathione-S-transferase pi
Funding
- NCI NIH HHS [CA85478, CA93533] Funding Source: Medline
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To determine the effects of glutathione-S-transferase pi (GSTpi) 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 GSTpi), but not of LNCaP cells ( which lack GSTpi expression) at concentrations below 1 muM. LNCaP cells stably transfected and expressed GSTpi (LNCaP/GSTpi) became sensitive to As2O3 growth inhibition. As2O3 arrested cell growth of DU-145, PC-3 and LNCaP/GSTpi cells in the G2/M phase of the cell cycle at low concentrations (<2 mu M), but did not induce apoptosis. At higher concentrations (10-20 mu M), As2O3 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/GSTp cells became insensitive to As2O3-induced apoptosis with reduced JNK activition. These data indicate that GST pi 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.
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