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 suppressed by 2-day treatment with troglitazone. EoL-1 cells treated with troglitazone were arrested and maintained in the G0/G1 phase in the cell cycle. This suppression correlated with the up-regulation of mRNA for p21WAF1/CIP1 cyclin-dependent kinase (Cdk) inhibitor. The inhibitory effects of troglitazone on cell proliferation and expression of p21 mRNA were observed in a human myelomonocytic cell line, U937, and a human myelomonoblastic cell line, KPB-M15. In addition, in EoL-1 cells, p21 protein was induced by troglitazone treatment and the induction was inhibited by protein synthesis inhibitor, cycloheximide. These data suggest that troglitazone inhibits cell proliferation in myeloid leukemia cell lines at least in part by induction of p21 Cdk inhibitor.
Sugimura
A
A
Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, 060-0812, Japan.
Kiriyama
Y
Y
Nochi
H
H
Tsuchiya
H
H
Tamoto
K
K
Sakurada
Y
Y
Ui
M
M
Tokumitsu
Y
Y
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects*; D002839:Chromans / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis* / Q000235:genetics; D004247:DNA / Q000032:analysis; D004791:Enzyme Inhibitors; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000378:metabolism / Q000473:pathology; D007951:Leukemia, Myeloid / Q000378:metabolism / Q000473:pathology*; D015479:Leukemia, Myelomonocytic, Acute / Q000378:metabolism / Q000473:pathology; D015477:Leukemia, Myelomonocytic, Chronic / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D000077288:Troglitazone; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D002839:Chromans; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D013844:Thiazoles; D045162:Thiazolidinediones; D004247:DNA; D000077288:Troglitazone