Triptolide down-regulates bcr-abl expression and induces apoptosis in chronic myelogenous leukemia cells

Leuk Lymphoma. 2004 Feb;45(2):373-6. doi: 10.1080/1042819031000139710.

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.

MeSH terms

  • Annexin A5 / pharmacology
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents, Alkylating / pharmacology
  • Apoptosis*
  • Blotting, Western
  • Cell Division
  • Cell Line, Tumor
  • Diterpenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Down-Regulation*
  • Enzyme Inhibitors / pharmacology
  • Epoxy Compounds
  • Fusion Proteins, bcr-abl / biosynthesis*
  • Humans
  • Inhibitory Concentration 50
  • K562 Cells
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology*
  • Phenanthrenes / pharmacology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Translocation, Genetic

Substances

  • Annexin A5
  • Antineoplastic Agents
  • Antineoplastic Agents, Alkylating
  • Diterpenes
  • Enzyme Inhibitors
  • Epoxy Compounds
  • Phenanthrenes
  • triptolide
  • Fusion Proteins, bcr-abl