In this study, we identified a new mechanism for the anti-proliferation of HCT15 colorectal cancer cells by troglitazone (TRO). Treating HCT15 cells with 20μM of TRO transiently increased extracellular signal regulated kinase (ERK) activity within 15min, 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.
Bibliographical noteFunding Information:
We would like to thank Drs G. Johnson and J.H. Kim for providing kinase inactive MEK and dominant inhibitory Raf-1 kinase construct, respectively. This work was supported by the following grants to K.-Y.C.: the 1999 Korean National Cancer Control Program, Ministry of Health and Welfare, Korea; grant 1999-1-212-001-5 from the basic research program, and Research Center for Biomedical Resources of the Korean Science and Engineering Foundation. J.-A.K., K.-S.P. and H.-I.K. are recipients of a scholarship from the Brain Korea 21 Project for Medical Science, Ministry of Education, Korea.
All Science Journal Classification (ASJC) codes
- Cancer Research