B5

Sulforaphane (SFN) induces apoptosis in tumor cells and inhibits inflammatory response through a poorly understood mechanism. Because the nuclear transcription factor nuclear factor κB (NF-κB) has been shown to suppress apoptosis and promote proliferation and is linked with inflammation and differentiation, we postulated that SFN modulates NF-κB activity and NF-κB-regulated geneexpression. Using human leukemia cell lines, we show that SFN potently inhibits inducible NF-κB activated by tumor necrosis factor-α (TNF-α). NF-κB suppression occurredthrough inhibition of IκBα phosphorylation, IκBα degradation, p65 phosphorylation and p65 nuclear translocation. This inhibition correlated with suppression of NF-κB-dependent genes involved in antiapoptosis (IAP1, XIAP, Bcl-2, and Bcl-xL), proliferation (cyclin D1 and c-Myc). Overall, our results suggestthat SFN inhibits NF-κB through inhibition of IκBα, leading to the suppression of expression of NF-κB-regulated gene products and enhancement of apoptosis induced by TNF-α.

First AACR Centennial Conference on Translational Cancer Medicine-- Nov 4-8, 2007; Singapore