Department of Plant Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
Mutat Res. 2010 Jan 5;683(1-2):123-30. doi: 10.1016/j.mrfmmm.2009.11.001.
Berberis lycium Royle (Berberidacea) from Pakistan and its alkaloids berberine and palmatine have been reported to possess beneficial pharmacological properties. In the present study, the anti-neoplastic activities of different B. lycium root extracts and the major constituting alkaloids, berberine and palmatine were investigated in p53-deficient HL-60 cells. The strongest growth inhibitory and pro-apoptotic effects were found in the n-butanol (BuOH) extract followed by the ethyl acetate (EtOAc)-, and the water (H(2)O) extract. The chemical composition of the BuOH extract was analyzed by TLC and quantified by HPLC. 11.1 microg BuOH extract (that was gained from 1mg dried root) contained 2.0 microg berberine and 0.3 microg/ml palmatine. 1.2 microg/ml berberine inhibited cell proliferation significantly, while 0.5 microg/ml palmatine had no effect. Berberine and the BuOH extract caused accumulation of HL-60 cells in S-phase. This was preceded by a strong activation of Chk2, phosphorylation and degradation of Cdc25A, and the subsequent inactivation of Cdc2 (CDK1). Furthermore, berberine and the extract inhibited the expression of the proto-oncogene cyclin D1. Berberine and the BuOH extract induced the acetylation of alpha-tubulin and this correlated with the induction of apoptosis. The data demonstrate that berberine is a potent anti-neoplastic compound that acts via anti-proliferative and pro-apoptotic mechanisms independent of genotoxicity.
来自巴基斯坦的小檗属植物（小檗科）及其生物碱小檗碱和巴马汀已被报道具有有益的药理特性。在本研究中，研究了不同小檗根提取物及其主要组成生物碱小檗碱和巴马汀对 p53 缺陷型 HL-60 细胞的抗肿瘤活性。在正丁醇（BuOH）提取物中发现最强的生长抑制和促凋亡作用，其次是乙酸乙酯（EtOAc）提取物和水（H2O）提取物。BuOH 提取物的化学成分通过 TLC 进行分析，并通过 HPLC 进行定量。11.1μg BuOH 提取物（从 1mg 干燥根中获得）含有 2.0μg 小檗碱和 0.3μg/ml 巴马汀。1.2μg/ml 小檗碱显著抑制细胞增殖，而 0.5μg/ml 巴马汀没有影响。小檗碱和 BuOH 提取物使 HL-60 细胞在 S 期积聚。这之前是 Chk2 的强烈激活，Cdc25A 的磷酸化和降解，以及随后的 Cdc2（CDK1）失活。此外，小檗碱和提取物抑制原癌基因 cyclin D1 的表达。小檗碱和 BuOH 提取物诱导α-微管蛋白的乙酰化，这与凋亡的诱导相关。数据表明，小檗碱是一种有效的抗肿瘤化合物，通过非遗传毒性的抗增殖和促凋亡机制发挥作用。
