Abstract #2967: Inhibition of macrophage migration inhibitory factor (MIF) expression by dietary components in colorectal cancer cells

It has been recognized that patients with inflammatory bowel disease (IBD) have increased risk of developing colon cancer. The consumption of dietary bioactive components that possess anti-inflammatory and anti-tumorigenic effects should be a suitable cancer prevention strategy for this patient group. MIF, a known pro-inflammatory cytokine, is one of the molecules that have been identified to have a dual activity in inflammation and tumorigenesis. Moreover, elevated levels of MIF in tissues and serum have been correlated with patients with IBD and colorectal cancer. In this study, we examined whether MIF was a molecular target of dietary components. Four dietary compounds, curcumin, quercetin, resveratrol, and sodium butyrate, were used to treat four human colorectal cancer cell lines, including HCT116, HT29, SW480 and KM12. The cell proliferation of these four cell lines was inhibited by all dietary compounds in a dose-dependent manner, as determined by MTS assay. The protein expression of MIF was also decreased in a dose-dependent manner in these colorectal cancer cells after 48 h treatment of these dietary compounds, except quercetin, as determined by Western blotting. The reduction of MIF protein expression in HCT116 and SW480 cells was not observed until 48 h and 72 h treatment of sodium butyrate. The mRNA level of MIF, as determined by semi-quantitative RT-PCR analysis, was also decreased in a dose-dependent manner after 48 h treatment of sodium butyrate in HCT116 cells. The mRNA level of MIF was decreased in 24 h in HCT116 and SW480 cells treated with sodium butyrate. In a MIF mRNA stability assay, addition of sodium butyrate didn\#8217;t change the MIF mRNA levels in actinomycin D-treated HCT116 cells, indicating that the reduction of MIF expression of sodium butyrate is regulated at the transcriptional level. Taken together, our results clearly demonstrate that dietary components can effectively inhibit MIF expression in colorectal cancer cells, along with evidence that MIF activity plays a role in the development of IBD and progression of colorectal cancer will lead a new strategy of targeting MIF for colorectal cancer prevention. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2967.