(-)Gossypol and its combination with imatinib induce apoptosis in human chronic myeloid leukemic cells.
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.
Meng
Yang
Y
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Li
Yan
Y
Li
Jing
J
Li
Hongyan
H
Fu
Jianjiang
J
Liu
Yue
Y
Liu
He
H
Chen
Xiaoguang
X
D017209:Apoptosis / Q000187:drug effects*; D001549:Benzamides; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004789:Enzyme Activation / Q000187:drug effects; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism; D006072:Gossypol / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000378:metabolism; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*; D051020:bcl-X Protein / Q000378:metabolism
C494811:BCL2L1 protein, human; D001549:Benzamides; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D010879:Piperazines; D019253:Proto-Oncogene Proteins c-bcl-2; D011743:Pyrimidines; D051020:bcl-X Protein; D000068877:Imatinib Mesylate; D045304:Cytochromes c; D016044:Fusion Proteins, bcr-abl; D053148:Caspase 3; D006072:Gossypol