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J Clin Pharm Ther. 2012 Feb;37(1):65-70. doi: 10.1111/j.1365-2710.2011.01251.x. Epub 2011 Mar 16.

Thiazolidenediones induce tumour-cell apoptosis through the Akt-GSK3β pathway.

Author information

1
Department of Pathophysiology, Medical College of Qingdao University, Qingdao University, Qingdao, China.

Abstract

WHAT IS KNOWN AND OBJECTIVE:

Prostate cancer is a major health threat for men. Thiazolidenediones (TZDs) are synthetic ligands of the peroxisome proliferator-activated receptor γ (PPARγ), and previous studies have shown that TZDs induce apoptosis of prostate cancer cells independently of PPARγ activation. However, the exact mechanism of these effects remains unknown. Our objective was to investigate the effects of TZDs on apoptosis and on the serine/threonine kinase pathway, Akt, and glycogen synthase kinase 3β (GSK3β).

METHODS:

LNCaP cells, a type of prostate cancer cells (derived from left supraclavicular lymph node of human prostrate carcinoma), were cultured in DMEM medium, and cell viability was evaluated with a colorimetric assay using MTT level. The total and phosphorylated protein level of Akt and GSK3β were detected by Western blotting.

RESULTS AND DISCUSSION:

The apoptosis-inducing effect of TZDs on prostate cancer cells involves the inhibition of Akt phosphorylation. Furthermore, TZDs induce inactivation of GSK3β, a multifunctional kinase that mediates essential events promoting prostate cancer development and acquisition of androgen independence. In addition, the GSK3β inhibitor lithium chloride sensitizes prostate cancer cells to TZDs cytotoxicity.

WHAT IS NEW AND CONCLUSION:

Our data suggest that modulation of Akt-GSK3β pathway is involved in the cell death pathway engaged by TZDs in prostate cancer cells. This reveals another possible mechanism of TZDs on apoptosis in prostate cancer. Inhibition of the Akt-GSK3β cascade may be a useful approach in prostate cancer.

[Indexed for MEDLINE]

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