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Title: Indole-3-carbinol-induced modulation of NF-kB signalling is breast cancer cell-specific and does not correlate with cell death
Authors: Moiseeva, Elena P.
Heukers, Raimond
First Published: 26-Jun-2007
Publisher: Springer Verlag
Citation: Breast Cancer Research and Treatment, 2007, 109(3), pp. 451-462
Abstract: 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-κB, 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-κB-regulated reporter gene expression was in the order HBL100 << MDA-MB-468 << MDA-MB-231. Upstream inhibition, using PI3K, EGFR or IKKβ inhibitors, resulted in cell-specific effects on expression of the NF-κB-regulated reporter gene and endogenous genes Bcl-xL, IκBα and IL-6, as well as on cell viability. The expression patterns of Rel and several NF-κB-regulated genes and the response to LY249002 in MDA-MB-468 cells contrasted with those in other cells. I3C induced NF-κB-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 TNFα induced NF-κB-regulated reporter gene expression, detected 5 h later, in MDA-MB-468, but not HBL100 cells. I3C induced NF-κB p65/p50 DNA binding at 6.5 h, preceded by association of IKKβ with the Src/EGFR complex and increased phospho-IκBα in MDA-MB468 cells. TNFα 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-κB was cell-specific. I3C influenced the NF-κB pathway in a cell-specific manner, which was not related to apoptosis. However, the combination of I3C and TNFα increased apoptosis in all cell lines.
DOI Link: 10.1007/s10549-007-9669-6
Type: Article
Description: This is the authors' final draft of the paper published as Breast Cancer Research and Treatment, 2--7, 109(3), pp.451-462. The final published version is available on, DOI: 10.1007/s10549-007-9669-6
Appears in Collections:Published Articles, Dept. of Cancer Studies and Molecular Medicine

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