期刊
LEUKEMIA RESEARCH
卷 30, 期 1, 页码 17-23出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.leukres.2005.05.023
关键词
berbamine; chronic myeloid leukemia; bcr/abl; apoptosis; caspase-3
Gleevec, which is an inhibitor of the bcr/abl tyrosine kinase, has been a remarkable success for the treatment of chronic myclogenous leukemia (CML). However, a significant proportion of patients chronically treated with Gleevec develop resistance. Here we describe the activity of a natural small molecular compound, berbamine from plant Berberis amurensis that can selectively induce cell death of both Gleevec-sensitive and -resistant Ph+ CML cells. The IC50 values of berbamine were 8.80 mu g/ml in Gleevec-sensitive Ph+ CML cells, 11.34 mu g/ml in Gleevec-resistant Ph+ CML cells, and 54.40 mu g/ml in Ph- KG-1 cells, respectively. Similarly, berbamine was also found to display a selective anti-proliferative activity of primary leukemia cells from CML patients, and its IC50 values were 4.20-10.50 mu g/ml in primary CML cells, and 185.20 mu g/ml in normal bone marrow cells, respectively. More importantly, our studies demonstrate that berbamine down-regulates p210 ber/abl oncoprotein level, and induces apoptosis of bcr/abl+ cells through caspase-3-dependent pathway. These data suggest that berbamine might be a novel bcr/abl inhibitor with potent anti-leukemia activity. (c) 2005 Elsevier Ltd. All rights reserved.
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