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KMID : 0371619990150010063
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Journal of Wonkwang Medical Science
1999 Volume.15 No. 1 p.63 ~ p.67
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Antiprolferative Effects of Lovastatin on Cancer Cells
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Lee Hwan-Bong
Jang Joung-Soon
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Abstract
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Background: Lovastatin which is a potent inhibitor of HMG-CoA reductase has antiproliferative effect on cancer cells. We investigated the cell cycle regulatory mechanism of anti-proliferative effect of lovastatin and its therapeutic value on cancer treatment.
Methods: MDA-MB-231, an ER negative breast cancer cell line and PC-3-M, an androgen independent prostate cancer cell line were grown up to use. We checked expression pattern of cell cycle regulatory proteins such as cyclins, cdk inhibitors including p21, cdks, RB and RB family protein p107 with lovastatin by Western blot analysis and immunoprecipitation.
Results: The proliferative tendency of breast cancer and prostate cancer cells was decreased with 10 μM lovastatin. Cyclin D1 was decreased, however p21, a cdk inhibitor was increased with lovastatin. There is no change in the protein level of cyclin E, cdk4 and cdk2. After 36 h incubation with lovastatin, RB and p107 were dephosphorylated and showed increased binding with transcription factor E2F1 and E2F4 respectively.
Conclusion: These results show that lovastatin has antiproliferative effects on breast and prostate cancer cells. The cell cycle regulatory effects of lovastatin come to G1 phase and those are mediated by cyclin D1 depression, p21 induction and decreased activity of cdk4. In accordance with them RB dephosphorylation and its sucessive binding with E2F1 seem to have important role in growth inhibitory effect of lovastatin. These data suggest that growth inhibitory activity of lovastatin by way of cell cycle regulation supports the therapeutic value for cancer treatment.
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KEYWORD
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Lovastatin, Cell cycle arrest, Cancer cells
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