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.
Kim
Jin-Ah
JA
Department of Biochemistry and Molecular Biology, College of Medicine, Yonsei University, Seoul, South Korea.
Park
Ki-Sook
KS
Kim
Ha-Il
HI
Oh
So-Young
SY
Ahn
Yongho
Y
Oh
Jong-Won
JW
Choi
Kang-Yell
KY
D015153:Blotting, Western; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002839:Chromans / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000187:drug effects* / Q000378:metabolism; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D019073:HT29 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D013997:Time Factors; D014157:Transcription Factors; D000077288:Troglitazone; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D050807:ets-Domain Protein Elk-1
C493956:CDKN1A protein, human; D002839:Chromans; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; C494112:ELK1 protein, human; D004791:Enzyme Inhibitors; D005419:Flavonoids; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D008156:Luciferases; D020928:Mitogen-Activated Protein Kinases; D001973:Bromodeoxyuridine; D000077288:Troglitazone; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one