Cell cycle arrest induced by the vitamin D-3 analog EB1089 in NCI-H929 myeloma cells is associated with induction of the cyclin-dependent kinase inhibitor p27
- Authors
- Park, WH; Seol, JG; Kim, ES; Jung, CW; Lee, CC; Binderup, L; Koeffler, HP; Kim, BK; Lee, YY
- Issue Date
- Feb-2000
- Publisher
- ACADEMIC PRESS INC
- Keywords
- vitamin D-3; analog; cell cycle; cyclin-dependent kinase inhibitor; p27; myeloma
- Citation
- EXPERIMENTAL CELL RESEARCH, v.254, no.2, pp 279 - 286
- Pages
- 8
- Journal Title
- EXPERIMENTAL CELL RESEARCH
- Volume
- 254
- Number
- 2
- Start Page
- 279
- End Page
- 286
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/47383
- DOI
- 10.1006/excr.1999.4735
- ISSN
- 0014-4827
1090-2422
- Abstract
- EB1089, a 1,25-dihydroxyvitamin D-3 analog, has been known to have potent antiproliferative properties in a variety of malignant cells in vitro and in vivo. In the present study, we analyzed the effect of EB1089 on human myeloma cell lines, EB1089 inhibited the proliferation of NCI-H929 cells and RPMI8226 cells in a dose-dependent manner among three myeloma cell lines tested. The antiproliferative effect of EB1089 on myeloma cells was related to the expression level of vitamin D receptor, To investigate the mechanism of the antiproliferative effect of EB1089, cell cycle analysis was attempted in EB1089-sensitive NCI-H929 cells, EB1089 (1 x 10(-8) M) efficiently induced G(1), arrest of the cell cycle. Analysis of G(1) regulatory proteins demonstrated that protein levels of CDK2, CDK4, cyclin D1, and cyclin A were decreased in a time-dependent manner, but not those of CDK6 and cyclin E, by EB1089, In addition, EB1089 (1 x 10(-8) M, 72 h) increased the protein level of the CDKI, p27 and markedly enhanced the binding of p27 with CDK2 compared to EB1089-untreated cells. Furthermore, the activity of CDK2-associated cyclin kinase was decreased, which was accompanied by the reduction of cyclin-D1-, cyclin-E-, and cyclin-A-associated kinase activities, resulting in the hypophosphorylation of Rb protein. These results suggest that EB1089 can inhibit the proliferation of human myeloma cells, especially NCI-H929 cells, via a G(1), block in association with the induction of p27 and the reduction of CDK2 activity, (C) 2000 Academic Press.
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