期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 18, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/ijms18091908
关键词
phenethyl isothiocyanate (PEITC); colitis associated colon cancer
资金
- National Institutes of Health [K99/R00AT4245]
- USDA National Institute of Food and Agriculture [1004817]
- NATIONAL CENTER FOR COMPLEMENTARY & ALTERNATIVE MEDICINE [R00AT004245] Funding Source: NIH RePORTER
We have previously reported alleviation of dextran sodium sulfate (DSS)-induced ulcerative colitis signs in phenethyl isothiocyanate (PEITC)-treated mice. Here we investigated chemoprotective activities of PEITC in mice with Azoxymethane-DSS induced colitis associated colon carcinogenesis. We also examined the molecular mediators associated with the PEITC effects using relevant cell lines. A 0.12% PEITC-enriched mouse-diet reduced mucosal and submucosal inflammation as well as glandular atypia by 12% and the frequency of adenocarcinoma by 17% with a concomitant improvement in overall disease activity indices compared to the diseased control group. Lipopolysaccharide-induced in vitro up-regulation of key mediators of inflammation, immune response, apoptosis, and cell proliferation were attenuated by 10 M PEITC. Three of these mediators showed concentration-dependent reduction in respective mRNAs. Furthermore, PEITC inhibited Nuclear factor kappa B1 (NFB1) proteins in a concentration-dependent manner. The NFB1 mRNA expression inversely correlated (r = -0.940, p = 0.013) with tri-methylation of lysine 27 on histone 3 near its promoter region in a time-dependent manner. These results indicate that PEITC may slow down the development of colon carcinogenesis in an inflammatory intestinal setting which is potentially associated with epigenetic modulation of NFB1 signaling.
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