Mutation research, 2010-01, Vol.683 (1), p.123-130
2010
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- Autor(en) / Beteiligte
- Titel
- Berberine and a Berberis lycium extract inactivate Cdc25A and induce α-tubulin acetylation that correlate with HL-60 cell cycle inhibition and apoptosis
- Ist Teil von
- Mutation research, 2010-01, Vol.683 (1), p.123-130
- Ort / Verlag
- Netherlands: Elsevier B.V
- Erscheinungsjahr
- 2010
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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 2O) 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-5107eISSN: 1873-135XDOI: 10.1016/j.mrfmmm.2009.11.001Titel-ID: cdi_proquest_miscellaneous_733713816
- Format
- –
- Schlagworte
- Acetylation, Apoptosis - drug effects, Berberine - pharmacology, Berberis - chemistry, Berberis lycium, Blotting, Western, Cancer, cdc25 Phosphatases - antagonists & inhibitors, cdc25 Phosphatases - metabolism, Cell Cycle - drug effects, Chromatography, High Pressure Liquid, Chromatography, Thin Layer, Comet Assay, Ethnopharmacology, HL-60 Cells, Humans, Phosphorylation - drug effects, Plant Extracts - pharmacology, Plant Roots - chemistry, Polar extract, Tubulin - metabolism