Berberine and a Berberis lycium extract inactivate Cdc25A and induce α-tubulin acetylation that correlate with HL-60 cell cycle inhibition and apoptosis

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• 作者：Musa Khan ; Benedikt Giessrigl ; Caroline Vonach ; Sibylle Madlener ; Sonja Prinz ; Irene Herbaceck ; Christine Hö ; lzl ; Sabine Bauer ; Katharina Viola ; Wolfgang Mikulits ; Rizwana Aleem Quereshi ; Siegfrie
• 关键词：Berberis lycium ; Polar extract ; Cancer ; Ethnopharmacology
• 刊名：Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis
• 出版年：2010
• 出版时间：5 January 2010
• 年：2010
• 卷：683
• 期：1-2
• 页码：123-130
• 全文大小：1090 K

文摘

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 (H₂O) extract.

The chemical composition of the BuOH extract was analyzed by TLC and quantified by HPLC. 11.1 μg BuOH extract (that was gained from 1 mg dried root) contained 2.0 μg berberine and 0.3 μg/ml palmatine. 1.2 μg/ml berberine inhibited cell proliferation significantly, while 0.5 μg/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 α-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.