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 are well-established, the potential antimigratory effects of triptolide have not been characterized.


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.
Johnson
Sara M
SM
Department of Surgery, The University of Texas Medical Branch, Galveston, Texas, USA.
Wang
Xiaofu
X
Evers
B Mark
BM
D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D016213:Cyclins / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004815:Epidermal Growth Factor; D004852:Epoxy Compounds / Q000494:pharmacology; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D009496:Neurotensin; D010616:Phenanthrenes / Q000494:pharmacology*; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism; D018121:Receptors, Cytokine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018179:Receptors, Thrombin / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D029757:Tripterygium; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D018906:Antineoplastic Agents, Alkylating; C527276:CXCR4 protein, human; D016213:Cyclins; D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; D016271:Proto-Oncogene Proteins c-myc; D019718:Receptors, CXCR4; D018121:Receptors, Cytokine; D018179:Receptors, Thrombin; D018125:Receptors, Transforming Growth Factor beta; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C001899:triptolide; D009496:Neurotensin; D004815:Epidermal Growth Factor; D051546:Cyclooxygenase 2