β-catenin-mediated transactivation and cell - cell adhesion pathways are important in curcumin (diferuylmethane)-induced growth arrest and apoptosis in colon cancer cells

Aruna S. Jaiswal, Benjamin P. Marlow, Nirupama Gupta, Satya Narayan

Research output: Contribution to journalArticle

314 Scopus citations

Abstract

The development of nontoxic natural agents with chemopreventive activity against colon cancer is the focus of investigation in many laboratories. Curcumin (feruylmethane), a natural plant product, possesses such chemopreventive activity, but the mechanisms by which it prevents cancer growth are not well understood. In the present study, we examined the mechanisms by which curcumin treatment affects the growth of colon cancer cells in vitro. Results showed that curcumin treatment causes p53- and p21-independent G2/M phase arrest and apoptosis in HCT-116(p53+/+), HCT-116(p53-/-) and HCT-116(p21-/-) cell lines. We further investigated the association of the β-catenin-mediated c-Myc expression and the cell-cell adhesion pathways in curcumin-induced G2/M arrest and apoptosis in HCT-116 cells. Results described a caspase-3-mediated cleavage of β-catenin, decreased transactivation of β-catenin/Tcf-Lef, decreased promoter DNA binding activity of the β-catenin/Tcf-Lef complex, and decreased levels of c-Myc protein. These activities were linked with decreased Cdc2/cyclin B1 kinase activity, a function of the G2/M phase arrest. The decreased transactivation of β-catenin in curcumin-treated HCT-116 cells was unpreventable by caspase-3 inhibitor Z-DEVD-fmk, even though the curcumin-induced cleavage of β-catenin was blocked in Z-DEVD-fmk pretreated cells. The curcumin treatment also induced caspase-3-mediated degradation of cell-cell adhesion proteins β-catenin, E-cadherin and APC, which were linked with apoptosis, and this degradation was prevented with the caspase-3 inhibitor. Our results suggest that curcumin treatment impairs both Wnt signaling and cell-cell adhesion pathways, resulting in G2/M phase arrest and apoptosis in HCT-116 cells.

Original languageEnglish (US)
Pages (from-to)8414-8427
Number of pages14
JournalOncogene
Volume21
Issue number55
DOIs
StatePublished - Dec 5 2002
Externally publishedYes

Keywords

  • β-catenin
  • Apoptosis
  • c-Myc
  • Caspase-3
  • Cell - cell adhesion
  • Curcumin
  • G/M arrest

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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