Mechanism of triptolide-induced apoptosis: effect on caspase activation and Bid cleavage and essentiality of the hydroxyl group of triptolide

  • Xianxi Wang
  • Ranyia Matta
  • Gang Shen
  • Leif D. Nelin
  • Dehua Pei
  • Yusen LiuEmail author
Original Article


Triptolide is a compound extracted from the Chinese herb Tripterygium wilfordii Hook. f. Triptolide has potent anticancer activity. However, the mechanisms by which triptolide exerts its anticancer activities remain unclear. To explore the molecular mechanisms involved in the anticancer activity of triptolide, we have examined the effect of triptolide on the growth of pancreatic carcinoma PANC-1 and cervical adenocarcinoma HeLa cells. We found that treatment of both HeLa and PANC-1 cells with triptolide potently suppressed cell growth and induced apoptosis, indicated by nuclear fragmentation and blebbing. In both HeLa and PANC-1 cells, apoptosis induced by triptolide was associated with activation of both caspase-3 and caspase-8, and cleavage of poly(ADP-ribose) polymerase and Bid. Moreover, in HeLa cells, caspase-9 is also significantly activated in response to triptolide. Overexpression of Bcl-2 in HeLa cells substantially attenuated triptolide-induced apoptosis. Interestingly, substitution of the 14-OH of triptolide with an acetyl group abrogated both its anticancer and its antiinflammatory activities. Our studies suggest that triptolide may exert its anticancer effects by initiating apoptosis through both death-receptor- and mitochondria-mediated pathways. Our results indicate that both the apoptosis-promoting and the antiinflammatory activities of triptolide depend on the 14-OH group.


Triptolide Apoptosis Caspase Cancer Chemotherapy 



Poly(ADP-ribose) polymerase


Dimethyl sulfoxide






Tumor necrosis factor-α


Phosphate-buffered saline


Propidium iodide


Fluorescein isothiocyanate



We thank Dr. Lili Liu for technical assistance and Dr. Xiantao Wang for providing valuable reagents. We are grateful to Drs. John Fidler and Lurong Zhang for helpful discussion. This work was supported by a National Institute of Allergy and Infectious Diseases (NIAID) grant (R01AI57798) and by the Columbus Children's Research Institute.


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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Xianxi Wang
    • 1
  • Ranyia Matta
    • 2
  • Gang Shen
    • 3
  • Leif D. Nelin
    • 1
  • Dehua Pei
    • 3
  • Yusen Liu
    • 1
    • 2
    Email author
  1. 1.Department of Pediatrics, Center for Developmental Pharmacology and Toxicology, Children's Research InstituteThe Ohio State UniversityColumbusUSA
  2. 2.Integrated Biomedical Science Graduate ProgramThe Ohio State UniversityColumbusUSA
  3. 3.Department of ChemistryThe Ohio State UniversityColumbusUSA

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