title: Triptolide inhibits colon-rectal cancer cells proliferation by induction of G1 phase arrest through upregulation of p21.
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.
authors.affiliation: 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.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Shen
authors.forename: Zhenggang
authors.initials: Z
authors.lastname: Yue
authors.forename: Zhifu
authors.initials: Z
authors.lastname: Yang
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.forename: Chunyan
authors.initials: C
authors.lastname: Xin
authors.forename: Yukun
authors.initials: Y
authors.lastname: Wang
authors.forename: Qibing
authors.initials: Q
authors.lastname: Mei
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D056750:Cyclin A1 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004365:Drugs, Chinese Herbal; D004852:Epoxy Compounds / Q000494:pharmacology; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D051268:GA-Binding Protein Transcription Factor / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells / Q000187:drug effects; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051822:T Cell Transcription Factor 1 / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C503745:CCNA1 protein, human; D056750:Cyclin A1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D004852:Epoxy Compounds; D051268:GA-Binding Protein Transcription Factor; C495661:GABPA protein, human; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; D010616:Phenanthrenes; D051822:T Cell Transcription Factor 1; C497576:TCF7 protein, human; C001899:triptolide; D051057:Proto-Oncogene Proteins c-akt; C495900:CDK4 protein, human; C495911:CDK6 protein, human; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1