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

Juanjuan Liu; Min Shen; Zhenggang Yue; Zhifu Yang; Meng Wang; Chen Li; Chunyan Xin; Yukun Wang; Qibing Mei; Zhipeng Wang

doi:10.1016/j.phymed.2012.02.014

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.

Authors

Juanjuan Liu¹, Min Shen, Zhenggang Yue, Zhifu Yang, Meng Wang, Chen Li, Chunyan Xin, Yukun Wang, Qibing Mei, Zhipeng Wang

Affiliation

¹ Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, China.

PMID: 22464014
DOI: 10.1016/j.phymed.2012.02.014

Abstract

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

Substances

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