Troglitazone activates p21Cip/WAF1 through the ERK pathway in HCT15 human colorectal cancer cells

In this study, we identified a new mechanism for the anti-proliferation of HCT15 colorectal cancer cells by troglitazone (TRO). Treating HCT15 cells with 20 microM of TRO transiently increased extracellular signal regulated kinase (ERK) activity within 15 min, and this subsequently induced p21Cip/WAF1 cell cycle regulator and localized in the nucleus. Raf-1 modification and MEK activation also occurred after TRO treatment, and Elk-1-dependent trans-reporter gene expression was concomitantly induced. The induction and nuclear localization of p21Cip/WAF1 by TRO were blocked by PD98059 pre-treatment, which suggested a role for the ERK pathway in p21Cip/WAF1 activation. TRO inhibited BrdU incorporation and no BrdU incorporation was observed in most p21Cip/WAF1-activated cells. Therefore, TRO regulates the proliferation of HCT15 cells at least partly by a mechanism involving the activation of p21Cip/WAF1.