Lovastatin-induced inhibition of HL-60 cell proliferation via cell cycle arrest and apoptosis
- Authors
- Park, WH; Lee, YY; Kim, ES; Seol, JG; Jung, CW; Lee, CC; Kim, BK
- Issue Date
- Jul-1999
- Publisher
- INT INST ANTICANCER RESEARCH
- Keywords
- lovastatin; cell cycle; cyclin-dependent kinase inhibitor; apoptosis; HL-60
- Citation
- ANTICANCER RESEARCH, v.19, no.4B, pp 3133 - 3140
- Pages
- 8
- Journal Title
- ANTICANCER RESEARCH
- Volume
- 19
- Number
- 4B
- Start Page
- 3133
- End Page
- 3140
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/47438
- ISSN
- 0250-7005
1791-7530
- Abstract
- An inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, lovastatin, induces growth arrest and cell death in a wide variety of malignant cells in vitro. We analyzed the effect of lovastatin on. myeloid leukemic cell lines. Lovastatin significantly inhibited the proliferation of 7 cell lines among II myeloid leukemic cell lines in a dose-dependent manner: In order to address the mechanism of antileukemic effect of lovastatin, cell cycle analysis was attempted in HL-60 cells, showing that lovastatin induced GI nn est in HL-60 cells following 72 h of drug exposure (1.5 mu M, 5 mu M and 10 mu M) in a dose-dependent manna: Analysis of GI regulatory proteins demonstrated that the protein levels of cyclin-dependent kinase (CDK) 5 CDK4, CDK6 and cyclin E were decreased after treatment with lovastatin (10 mu M) in a time-dependent manner, but not cyclin DI. In addition lovastatin increased the protein level of the cyclin-dependent kinase inhibitor (CDKI), p27, and markedly enhanced the binding of p27 with CDK2 and CDK4 more than CDK6 after 24 h exposure. At higher doses of lovastatin (50 mM 100 mM, 200 mM), a significant apoptosis was observed as evidenced by FAGS analysis with annexin V staining, which was associated with downregulation of Bcl-2 protein. These results suggest that lovastatin inhibits the proliferation of myeloid leukemic cells via GI arrest in association with p27 induction and is an effective inducer of apoptosis in HL-60 cells.
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