Triptolide Inhibits Proliferation and Migration of Colon Cancer Cells by Inhibition of Cell Cycle Regulators and Cytokine Receptors

Background Phytochemicals are an important source of emerging preventive and therapeutic agents for cancer. Triptolide/PG490, an extract of the Chinese herb Tripterygium wilfordii Hook F, is a potent anti-inflammatory agent that also possesses anticancer activity. While its antiproliferative effects...

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Bibliographic Details
Published in:The Journal of surgical research 2011-06, Vol.168 (2), p.197-205
Main Authors: Johnson, Sara M., M.D, Wang, Xiaofu, B.S, Evers, B. Mark, M.D
Format: Article
Language:English
Subjects:
Antineoplastic Agents, Alkylating - pharmacology
Biological and medical sciences
cell cycle
Cell Movement - drug effects
Cell Proliferation - drug effects
chemokine
colorectal cancer
Cyclins - metabolism
Cyclooxygenase 2 - metabolism
Diterpenes - pharmacology
Drug Evaluation, Preclinical
Epidermal Growth Factor
Epoxy Compounds - pharmacology
Gastroenterology. Liver. Pancreas. Abdomen
General aspects
growth factor receptors
HCT116 Cells
herbal extract
HT29 Cells
Humans
Medical sciences
Neurotensin
Phenanthrenes - pharmacology
Proto-Oncogene Proteins c-myc - antagonists & inhibitors
Proto-Oncogene Proteins c-myc - metabolism
Receptors, CXCR4 - metabolism
Receptors, Cytokine - antagonists & inhibitors
Receptors, Cytokine - metabolism
Receptors, Thrombin - metabolism
Receptors, Transforming Growth Factor beta - metabolism
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Surgery
Tripterygium
triptolide
Tumors
Vascular Endothelial Growth Factor A - metabolism
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Summary:Background Phytochemicals are an important source of emerging preventive and therapeutic agents for cancer. Triptolide/PG490, an extract of the Chinese herb Tripterygium wilfordii Hook F, is a potent anti-inflammatory agent that also possesses anticancer activity. While its antiproliferative effects are well-established, the potential antimigratory effects of triptolide have not been characterized. Material and Methods Effects of triptolide on the proliferation and invasion of colon cancer cells and expression of cancer-related genes and proteins were assessed. Results Triptolide potently inhibited HT29 and HCT116 colon cancer cell growth and reduced basal and stimulated HCT116 migration through collagen by 65% to 80%. Triptolide inhibited mRNA expression of the positive cell cycle regulatory genes c - myc, and A, B, C, and D-type cyclins in multiple colon cancer cell lines. Additionally, we show that triptolide treatment decreased expression of VEGF and COX-2, which promote cancer progression and invasion, and inhibited the expression of multiple cytokine receptors potentially involved in cell migration and cancer metastasis, including the thrombin receptor, CXCR4, TNF receptors, and TGF-β receptors. Conclusions Triptolide is a potent inhibitor of colon cancer proliferation and migration in vitro . The down-regulation of multiple cytokine receptors, in combination with inhibition of COX-2 and VEGF and positive cell cycle regulators, may contribute to the antimetastatic action of this herbal extract.
ISSN:0022-4804
1095-8673
DOI:10.1016/j.jss.2009.07.002