Lin Chin-Chung, Lin Shuw-Yun, Chung Jing-Gung, Lin Jing-Pin, Chen Guang-Wei, Kao Shung-Te
Graduate Institute of Chinese Medical Science, China Medical University, Taiwan, Taichung City 404, Taiwan, ROC.
Anticancer Res. 2006 Mar-Apr;26(2A):1097-104.
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.
小檗碱具有广泛的生物学作用，表明其可能在癌症预防中发挥作用。此前有报道称，小檗碱可诱导细胞周期停滞，不仅在G0/G1期，而且在G2/M期呈剂量依赖性。然而，小檗碱诱导白血病细胞G2/M期停滞的机制尚未完全明确。在本研究中，我们研究了天然存在的小檗碱（黄连的主要成分）对人早幼粒细胞白血病HL-60细胞和小鼠骨髓单核细胞白血病WEHI-3细胞的细胞周期以及CDK1、细胞周期蛋白B1、14-3-3σ、Wee1和Cdc25c表达的影响。流式细胞术分析表明，小檗碱在两种受试细胞系中均诱导G2/M期停滞。小檗碱在两种受试细胞系中诱导的G2/M期停滞伴随着Wee1和14-3-3σ水平的升高，但Cdc25c、CDK1和细胞周期蛋白B1水平的降低。然而，蛋白质印迹分析显示CDK2表达未受影响。小檗碱通过抑制细胞周期蛋白B1和促进Wee1在两种受试细胞中诱导G2/M期停滞。
