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 language | English (US) |
---|---|
Pages (from-to) | 17-23 |
Number of pages | 7 |
Journal | Leukemia Research |
Volume | 30 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2006 |
Externally published | Yes |
Keywords
- Apoptosis
- Bcr/abl
- Berbamine
- Caspase-3
- Chronic myeloid leukemia
ASJC Scopus subject areas
- Hematology
- Oncology
- Cancer Research