Abstract
Thiazolidinediones (TZDs) dramatically reduce the growth of human prostate cancer cells in vitro and in vivo. To determine whether the antitumor effects of TZDs were due in part to changes in the MEK/Erk signaling pathway, we examined the regulation of Erk phosphorylation by the TZD troglitazone within the PC-3 and C4-2 human prostate cancer cell lines. Western blot analysis revealed troglitazone-induced phosphorylation of Erk in both PC-3 and C4-2 cells. Troglitazone-induced increases in Erk phosphorylation were suppressed by the MEK inhibitor U0126 but not by the PPARγ antagonist GW9662. Pretreatment with U0126 did not alter the ability of troglitazone to regulate expression of two proteins that control cell cycle, p21, and c-Myc. Troglitazone was also still effective at reducing PC-3 proliferation in the presence of U0126. Therefore, our data suggest that troglitazone-induced Erk phosphorylation does not significantly contribute to the antiproliferative effect of troglitazone.
Highlights
The thiazolidinediones (TZDs) are a group of high-affinity agonists for the peroxisome proliferator activated receptor gamma (PPARγ) that includes the compounds ciglitazone, troglitazone (Rezulin), rosiglitazone (Avandia), and pioglitazone (Actos) [1, 2]
Our preliminary studies suggest that U0126 does not enhance the ability of troglitazone to induce apoptosis within PC-3 cells
Our data indicate that troglitazone induce Erk phosphorylation in human prostate cancer cells via a PPARγindependent signaling pathway
Summary
The thiazolidinediones (TZDs) are a group of high-affinity agonists for the peroxisome proliferator activated receptor gamma (PPARγ) that includes the compounds ciglitazone, troglitazone (Rezulin), rosiglitazone (Avandia), and pioglitazone (Actos) [1, 2]. TZDs have been reported to regulate Erk activation in normal epithelium and cancer cells Both troglitazone and ciglitazone increase Erk phosphorylation in the rat GN4 liver epithelial cells [29]. Ciglitazone increases Erk phosphorylation and induces apoptosis in the HT-29 colon cancer cell line [32]. In NCI-H23 human nonsmall cell lung cancer cells, troglitazone-stimulated increases in apoptosis were accompanied by an elevation in Erk 1/2 phosphorylation [33]. To determine whether the anti-proliferative effects of troglitazone in prostate cancer cells are associated with altered Erk 1/2 activity, we examined whether troglitazone regulates Erk phosphorylation in the present study. Our data indicate that troglitazone does enhance Erk phosphorylation This increase in Erk phosphorylation plays a minimal role in the anti-proliferative effect of troglitazone within human prostate cancer cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
