Triptolide inhibits proliferation and migration of colon cancer cells by inhibition of cell cycle regulators and cytokine receptors

Sara M. Johnson, Xiaofu Wang, B. Mark Evers

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)197-205
Number of pages9
JournalJournal of Surgical Research
Volume168
Issue number2
DOIs
StatePublished - Jun 15 2011

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Cytokine Receptors
Colonic Neoplasms
Cell Cycle
Vascular Endothelial Growth Factor A
Cyclin C
Tripterygium
CXCR4 Receptors
Cyclin D
Thrombin Receptors
cdc Genes
Neoplasms
triptolide
Tumor Necrosis Factor Receptors
Neoplasm Genes
Phytochemicals
Regulator Genes
Cell Movement
Anti-Inflammatory Agents
Collagen
Down-Regulation

Keywords

  • cell cycle
  • chemokine
  • colorectal cancer
  • growth factor receptors
  • herbal extract
  • triptolide

ASJC Scopus subject areas

  • Surgery

Cite this

Triptolide inhibits proliferation and migration of colon cancer cells by inhibition of cell cycle regulators and cytokine receptors. / Johnson, Sara M.; Wang, Xiaofu; Evers, B. Mark.

In: Journal of Surgical Research, Vol. 168, No. 2, 15.06.2011, p. 197-205.

Research output: Contribution to journalArticle

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abstract = "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.",
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