Troglitazone suppresses cell growth of myeloid leukemia cell lines by induction of p21WAF1/CIP1 cyclin-dependent kinase inhibitor

In a human eosinophilic leukemia cell line, EoL-1, cell proliferation was s uppressed by a-day treatment with troglitazone, EoL-1 cells treated with tr oglitazone were arrested and maintained in the G0/G1 phase in the cell cycl e. This suppression correlated with the up-regulation of mRNA for p21WAF1/C IP1 cyclin-dependent kinase (Cdk) inhibitor. The inhibitory effects of trog litazone on cell proliferation and expression of p21 mRNA were observed in a human myelomonocytic cell line, U937, and a human myelomonoblastic cell l ine, KPB-M15. In addition, in EoL-1 cells, p21 protein was induced by trogl itazone treatment and the induction was inhibited by protein synthesis inhi bitor, cycloheximide. These data suggest that troglitazone inhibits cell pr oliferation in myeloid leukemia cell lines at least in part by induction of p21 Cdk inhibitor. (C) 1999 Academic Press.