(-)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 DeltaPsim 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.