title: Triptolide down-regulates bcr-abl expression and induces apoptosis in chronic myelogenous leukemia cells.
abstract: 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.
authors.affiliation: ZheJiang University, Institute of Hematology, HangZhou, ZheJiang, China. louyinjun@yahoo.com.cn
authors.forename: Yin Jun
authors.initials: YJ
authors.lastname: Lou
authors.forename: Jie
authors.initials: J
authors.lastname: Jin
mesh_terms: 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
chemical_list: 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