Berbamine: A novel inhibitor of bcr/abl fusion gene with potent anti-leukemia activity

Rongzhen Xu, Qinghua Dong, Yingzi Yu, Xiaoying Zhao, Xiaoxian Gan, Dong Wu, Qinghua Lu, Xiaohua Xu, Xiao Fang Yu

Research output: Contribution to journalArticlepeer-review

Abstract

Gleevec, which is an inhibitor of the bcr/abl tyrosine kinase, has been a remarkable success for the treatment of chronic myelogenous 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 μg/ml in Gleevec-sensitive Ph+ CML cells, 11.34 μg/ml in Gleevec-resistant Ph+ CML cells, and 54.40 μg/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 μg/ml in primary CML cells, and 185.20 μg/ml in normal bone marrow cells, respectively. More importantly, our studies demonstrate that berbamine down-regulates p210 bcr/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.

Original languageEnglish (US)
Pages (from-to)17-23
Number of pages7
JournalLeukemia Research
Volume30
Issue number1
DOIs
StatePublished - Jan 2006

Keywords

  • Apoptosis
  • Bcr/abl
  • Berbamine
  • Caspase-3
  • Chronic myeloid leukemia

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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