Sulindac suppresses β-catenin expression in human cancer cells

Anjia Han, Zibo Song, Chang Tong, Dong Hu, Xiuli Bi, Leonard H. Augenlicht, Wancai Yang

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Sulindac has been reported to be effective in suppressing tumor growth through the induction of p21WAF1/cip1 in human, animal models of colon cancer and colon cancer cells. In this study, we treated human breast cancer cell line MCF-7 and lung cancer cell line A549 as well as colon cancer cell line SW620 with sulindac to observe the effects of sulindac in other tissue sites. In all cell lines, proliferation was significantly inhibited by sulindac after 24 and 72 h of treatment. Apoptosis was induced by sulindac in both lung cancer cells and colon cancer cells but was not induced in breast cancer cells. Western blots showed that p21 protein level were induced by sulindac in lung cancer cells and colon cancer cells, but not in breast cancer cells. However, the suppression of β-catenin, a key mediator of Wnt signaling pathway, was seen in all three cell lines with sulindac administration. Further studies revealed that transcriptional activities of β-catenin were significantly inhibited by sulindac and that the inhibition was sulindac dosage-dependent. The transcriptional targets of β-catenin, c-myc, cyclin D1 and cdk 4 were also dramatically downregulated. In conclusion, our data demonstrated that the efficacy of sulindac in the inhibition of cell proliferation (rather than the induction of apoptosis) might be through the suppression of β-catenin pathway in human cancer cells.

Original languageEnglish (US)
Pages (from-to)26-31
Number of pages6
JournalEuropean Journal of Pharmacology
Volume583
Issue number1
DOIs
StatePublished - Mar 31 2008

Keywords

  • Apoptosis
  • Cancer
  • Proliferation
  • Sulindac
  • p21WAF1/cip1
  • β-catenin

ASJC Scopus subject areas

  • Pharmacology

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