Low concentrations of resveratrol inhibit Wnt signal throughput in colon-derived cells: Implications for colon cancer prevention

Christopher Hope, Kestutis Planutis, Marina Planutiene, Mary P. Moyer, Karanjodh S. Johal, Jaesung Woo, Calista Santoso, Joseph A. Hanson, Randall F. Holcombe

Research output: Contribution to journalArticlepeer-review

118 Scopus citations

Abstract

Resveratrol is a bioflavonoid which is known to inhibit cell proliferation and induce apoptosis in cancer cell lines at concentrations above 50 μM. It also has colon cancer prevention activity in mouse models and possibly in humans. We have examined the effects of low concentrations of resveratrol on a specific signaling pathway, the Wnt pathway, which is activated in over 85% of sporadic colon cancers. Two colon cancer (HT29 and RKO) and one normal mucosa-derived (NCM460) cell lines were utilized. Cell proliferation was not affected by resveratrol at ≤40 μM for HT29 and NCM460 and ≤20 μM for RKO though Wnt signal throughput, as measured by a reporter construct, was reduced in RKO and NCM460 at concentrations as low as 10 μM (p < 0.001). This effect was most easily appreciated following Wnt pathway stimulation with Wnt3a conditioned medium and LEF1 or LEF1/β-catenin transfection. Resveratrol did not inhibit Wnt throughput in mutationally activated HT29. Low concentrations of resveratrol significantly decreased the amount and proportion of β-catenin in the nucleus in RKO (p = 0.002) and reduced the expression of lgs and pygoI, regulators of β-catenin localization, in all cells lines. Thus, at low concentrations, in the absence of effects on cell proliferation, resveratrol significantly inhibits Wnt signaling in colon-derived cells which do not have a basally activated Wnt pathway. This inhibitory effect may be due in part to regulation of intracellular β-catenin localization.

Original languageEnglish (US)
Pages (from-to)S52-S61
JournalMolecular Nutrition and Food Research
Volume52
Issue numberSUPPL. 1
DOIs
StatePublished - Jun 2008
Externally publishedYes

Keywords

  • Colon cancer
  • Pygopus
  • Resveratrol
  • Wnt pathway
  • β-catenin

ASJC Scopus subject areas

  • Biotechnology
  • Food Science

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