Triptolide inhibits colon-rectal cancer cells proliferation by induction of G1 phase arrest through upregulation of p21

Phytomedicine. 2012 Jun 15;19(8-9):756-62. doi: 10.1016/j.phymed.2012.02.014. Epub 2012 Mar 29.


Triptolide, a diterpene triepoxide compound extracted from the traditional Chinese medicine herb Tripterygium wilfordii Hook F., is a potential cancer chemotherapeutic for tumors. However, the mechanism of anti-proliferative mechanism of triptolide in colon cancer cells is not entirely clear. Triptolide markedly inhibited HT29 and SW480 cells proliferation in a dose- and time-dependent manner. Triptolide decreased ERK and AKT phosphorylation, and GABPα expression in colon cancer cells. Beta-catenin expression and phosphorylation were not altered by incubation of triptolide. However, we found that triptolide repressed expression of LEF/TCF. Although it did not significantly affect cells apoptosis, triptolide induced G1 phase arrest dose-dependently. Further detection for the expression of cell cycle-related proteins suggesting that triptolide stimulate expression of p21 and repress cyclin A1. Increased p21 binded to CDK4/CDK6, therefore blocked function of CDK4/CDK6, and subsequently contribute to the G1 arrest. These data suggested that triptolide is a potential agent for treatment of colon cancer, and its anti-proliferation effect mainly occur through G1 phase arrest.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Cyclin A1 / metabolism
  • Cyclin-Dependent Kinase 4 / metabolism
  • Cyclin-Dependent Kinase 6 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • Diterpenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Drugs, Chinese Herbal
  • Epoxy Compounds / pharmacology
  • G1 Phase Cell Cycle Checkpoints / drug effects*
  • GA-Binding Protein Transcription Factor / metabolism
  • Gene Expression Regulation, Neoplastic
  • HT29 Cells / drug effects
  • Humans
  • Lymphoid Enhancer-Binding Factor 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Phenanthrenes / pharmacology*
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • T Cell Transcription Factor 1 / genetics
  • Up-Regulation / drug effects


  • Antineoplastic Agents, Phytogenic
  • CCNA1 protein, human
  • Cyclin A1
  • Cyclin-Dependent Kinase Inhibitor p21
  • Diterpenes
  • Drugs, Chinese Herbal
  • Epoxy Compounds
  • GA-Binding Protein Transcription Factor
  • GABPA protein, human
  • LEF1 protein, human
  • Lymphoid Enhancer-Binding Factor 1
  • Phenanthrenes
  • T Cell Transcription Factor 1
  • TCF7 protein, human
  • triptolide
  • Proto-Oncogene Proteins c-akt
  • CDK4 protein, human
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1