Triptolide down-regulates bcr-abl expression and induces apoptosis in chronic myelogenous leukemia cells.
Interest in exploiting traditional medicines for prevention or treatment of cancer is increasing. Extracts from the herb Tripterygium wilfordii hook F have been used in China for centuries to treat immune-related disorders. Recently it was reported that triptolide, a purified compound from Tripterygium, possessed antitumor properties and induced apoptosis in a variety of malignant cell lines. K562 cells are usually resistant to apoptosis induction, probably because of the expression of bcr-abl, the hybrid gene characteristic of the Philadelphia chromosome t (9;22). Present studies demonstrate that triptolide inhibited K562 cells proliferation and induced apoptosis in a dose and time-dependent manner. The growth-inhibitory IC50 value for triptolide treatment was 40 ng/ml. Characteristic apoptotic features were confirmed by morphology, internucleosomal DNA fragmentation, and Annexin V Staining. Significantly, triptolide-induced apoptosis of K562 cells was associated with a decline in bcr-abl expression levels, at the concentrations of 20 ng/ml, 40 ng/ml and 80 ng/ml, triptolide was able to decrease the expression of bcr-abl down to 50%, 30% and 20% respectively of the basal value after 72 h. Our findings strongly suggest that triptolide might be an effective therapeutic agent against CML cells.
Lou
Yin Jun
YJ
ZheJiang University, Institute of Hematology, HangZhou, ZheJiang, China. louyinjun@yahoo.com.cn
Jin
Jie
J
D017304:Annexin A5 / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D002455:Cell Division; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004852:Epoxy Compounds; D016044:Fusion Proteins, bcr-abl / Q000096:biosynthesis*; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism / Q000473:pathology*; D010616:Phenanthrenes / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014178:Translocation, Genetic
D017304:Annexin A5; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D004224:Diterpenes; D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D010616:Phenanthrenes; C001899:triptolide; D016044:Fusion Proteins, bcr-abl