Indole-3-carbinol-induced modulation of NF-kappaB signalling is breast cancer cell-specific and does not correlate with cell death

Elena P Moiseeva, Raimond Heukers

Research output: Contribution to JournalArticleAcademicpeer-review


Indole-3-carbinol (I3C), a dietary chemopreventive compound, induces cell death in human breast cancer cells by modulating activities of Src and epidermal growth factor receptor (EGFR). The effect of I3C on NF-kappaB, constitutively activated in breast cancer cells, was investigated. Nuclear extracts of MDA-MB-468, MDA-MB-231 and HBL100 cells contained all of the Rel proteins with similar expression patterns in the latter two. The level of NF-kappaB-regulated reporter gene expression was in the order HBL100 < MDA-MB-468 < MDA-MB-231. Upstream inhibition, using PI3K, EGFR or IKKbeta inhibitors, resulted in cell-specific effects on expression of the NF-kappaB-regulated reporter gene and endogenous genes Bcl-xL, IkappaBalpha and IL-6, as well as on cell viability. The expression patterns of Rel and several NF-kappaB-regulated genes and the response to LY249002 in MDA-MB-468 cells contrasted with those in other cells. I3C induced NF-kappaB-regulated reporter gene expression at 12 h in MDA-MB-468 cells. Conversely, it was reduced at 24 h in HBL100 cells. I3C treatment for 6 h alone or in combination with TNFalpha induced NF-kappaB-regulated reporter gene expression, detected 5 h later, in MDA-MB-468, but not HBL100 cells. I3C induced NF-kappaB p65/p50 DNA binding at 6.5 h, preceded by association of IKKbeta with the Src/EGFR complex and increased phospho-IkappaBalpha in MDA-MB468 cells. TNFalpha increased I3C-induced apoptosis in MDA-MB-468 and MDA-MB-231 cells. It also induced apoptosis, enhanced by I3C, in HBL100 cells. Hence, regulation of constitutive NF-kappaB was cell-specific. I3C influenced the NF-kappaB pathway in a cell-specific manner, which was not related to apoptosis. However, the combination of I3C and TNFalpha increased apoptosis in all cell lines.

Original languageEnglish
Pages (from-to)451-62
Number of pages12
JournalBreast Cancer Research and Treatment
Issue number3
Publication statusPublished - Jun 2008
Externally publishedYes


  • Anticarcinogenic Agents
  • Apoptosis
  • Breast Neoplasms
  • Cell Line, Tumor
  • Cell Survival
  • Chromones
  • DNA
  • Female
  • Humans
  • Indoles
  • Morpholines
  • NF-kappa B
  • Signal Transduction
  • Tumor Necrosis Factor-alpha
  • Journal Article
  • Research Support, Non-U.S. Gov't


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