(–)Gossypol and its combination with imatinib induce apoptosis in human chronic myeloid leukemic cells

Abstract

Chronic myeloid leukemia (CML) is characterized by the presence of chimeric protein BCR-ABL associated with high tyrosine kinase (TK) activity, which leads to cell tumorogenicity, resistance to apoptosis, and differentiation. Gossypol is a natural polyphenolic compound isolated from cottonseed and has antiproliferative activity in a variety of cancer cell lines. (–)Gossypol is proved the potent component. Here we examined the growth inhibitory effect of (–)gossypol and its combination with imatinib in K562 cells. (–)Gossypol inhibited cell growth, promoted apoptosis, induced ΔΨ_m loss, and cytochrome C release. Furthermore, (–)gossypol had a synergistic inhibitory effect on growth in K562 cells when combined with imatinib. Enhanced apoptosis, cytochrome C release, and caspase 3 cleavage as well as noticeable decrease of Mcl-1 and Bcl-XL were observed in K562 cells treated with both (–)gossypol and imatinib. These results suggest that (–)gossypol induced apoptosis in K562 cells through a mitochondria pathway and that the combination of imatinib and (–)gossypol might be an effective treatment for CML.

Keywords:

• (–)Gossypol
• imatinib
• chronic myeloid leukemia
• apoptosis