Triptolide induces apoptosis in endometrial cancer via a p53‑independent mitochondrial pathway

Mol Med Rep. 2014 Jan;9(1):39-44. doi: 10.3892/mmr.2013.1783. Epub 2013 Nov 8.


Triptolide (TP), the primary active component purified from the traditional Chinese herbal medicine Tripterygium wilfordii Hook. F (TWHF), has been shown to possess antitumor activity in several types of solid tumors. In the present study, we investigated the antitumor effect of TP in human endometrial cancer cells (HEC-1B) and elucidated its possible underlying mechanisms. HEC-1B cells were treated with various doses of TP (10, 20, 40, 80, 160 and 320 nM), and the cell viability was assessed by Cell Counting Kit-8 (CCK-8) and flow cytometric analysis. Results indicated that TP inhibited the proliferation of HEC-1B cells in a dose- and time‑dependent manner. To further investigate its mechanisms, the levels of apoptosis and the changes in caspase-3/9 expression in HEC-1B cells by pretreatment with z-VAD-fmk, a pan-caspase inhibitor, were detected by CCK-8 and western blotting. The cytotoxic effects of TP were significantly inhibited by z-VAD‑fmk. At the molecular level, TP did not effectively activate the p53 signaling pathway, but upregulated caspase-3/9 and downregulated bcl-2 without changing the bax level. Our studies revealed that TP has an effect on the apoptotic ability of endometrial cancer cells via a p53-independent mitochondrial pathway, presenting a novel strategy to evade drug resistance in tumorigenesis. The ability of TP to be a potential chemotherapeutic agent for endometrial cancer should be considered.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology
  • Antineoplastic Agents, Alkylating / pharmacology*
  • Apoptosis / drug effects*
  • Caspase 3 / chemistry
  • Caspase 3 / metabolism
  • Caspase 9 / chemistry
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Diterpenes / pharmacology*
  • Down-Regulation / drug effects
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / pathology
  • Epoxy Compounds / pharmacology
  • Female
  • Humans
  • Mitochondria / metabolism*
  • Phenanthrenes / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction / drug effects
  • Tumor Suppressor Protein p53 / metabolism*
  • Up-Regulation / drug effects
  • bcl-2-Associated X Protein / metabolism


  • Amino Acid Chloromethyl Ketones
  • Antineoplastic Agents, Alkylating
  • Diterpenes
  • Epoxy Compounds
  • Phenanthrenes
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • triptolide
  • Caspase 3
  • Caspase 9