Down-regulation of cyclin B1 and up-regulation of Wee1 by berberine promotes entry of leukemia cells into the G2/M-phase of the cell cycle.
Berberine has a wide range of biological actions that suggest it may be of use in cancer prevention. It was previously reported that berberine induced cell cycle arrest, not only at the G0/G1-phase, but also at the G2/M-phase in a dose-dependent manner. However, the mechanism of berberine-induced G2/M-phase arrest in leukemia cells is not fully understood. In the present study, the effects of the naturally occurring berberine (the major constituent of Coptis chinensis) on the cell cycle, as well as on CDK1, cyclin B1, 14-3-3sigma, Wee1 and Cdc25c expressions, were investigated in the human promyelocytic leukemia HL-60 cells and in the murine myelomonocytic leukemia WEHI-3 cells. The flow cytometry assays indicated that berberine induced G2/M-phase arrest in both examined cell lines. The berberine-induced G2/M-phase arrest in both examined cell lines was accompanied by increased levels of Wee1 and 14-3-3sigma, but decreased levels of Cdc25c, CDK1 and cyclin B1. However, CDK2 expression was not affected as revealed by Western blotting assay. Berberine induced G2/M arrest in both the examined cells via the inhibition of cyclin B1 and the promotion of Wee1.
Lin
Chin-Chung
CC
Graduate Institute of Chinese Medical Science, China Medical University, Taiwan, Taichung City 404, Taiwan, ROC.
Lin
Shuw-Yun
SY
Chung
Jing-Gung
JG
Lin
Jing-Pin
JP
Chen
Guang-Wei
GW
Kao
Shung-Te
ST
D048948:14-3-3 Proteins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D015153:Blotting, Western; D016203:CDC2 Protein Kinase / Q000096:biosynthesis / Q000235:genetics; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D019926:Cyclin B / Q000096:biosynthesis* / Q000235:genetics; D056744:Cyclin B1; D019927:Cyclin E / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects; D020687:cdc25 Phosphatases / Q000096:biosynthesis / Q000235:genetics
D048948:14-3-3 Proteins; C534699:CCNB1 protein, human; D018797:Cell Cycle Proteins; D019926:Cyclin B; D056744:Cyclin B1; D019927:Cyclin E; D009687:Nuclear Proteins; D001599:Berberine; D011505:Protein-Tyrosine Kinases; C499349:WEE1 protein, human; D016203:CDC2 Protein Kinase; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases