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Dual effects of glutathione-S-transferase π on As2O3 action in prostate cancer cells: enhancement of growth inhibition and inhibition of apoptosis

Oncogene volume 23, pages 3945–3952 (2004)Cite this article

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 μ M. LNCaP cells stably transfected and expressed GSTπ (LNCaP/GSTπ) became sensitive to As2O3 growth inhibition. As2O3 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 μ M), but did not induce apoptosis. At higher concentrations (10–20 μ 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/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.

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Acknowledgements

This work was partly supported by NIH Grants CA93533 and CA85478, and Samuel Waxman Cancer Research Foundation.

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  1. Division of Hematology/Oncology, Department of Medicine, Mount Sinai School of Medicine, New York, 10029, NY, USA

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

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Correspondence to Yongkui Jing.

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Lu, M., Xia, L., Luo, D. et al. Dual effects of glutathione-S-transferase π on As2O3 action in prostate cancer cells: enhancement of growth inhibition and inhibition of apoptosis. Oncogene 23, 3945–3952 (2004). https://doi.org/10.1038/sj.onc.1207500

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