Abstract
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 μM PEITC. Three of these mediators showed concentration-dependent reduction in respective mRNAs. Furthermore, PEITC inhibited Nuclear factor kappa B1 (NFκB1) proteins in a concentration-dependent manner. The NFκB1 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 NFκB1 signaling.
Highlights
Colorectal cancer (CRC) is second among various cancers in terms of causing deaths in the United States, and it resulted in an estimated healthcare expenditure of $14 billion in 2014
Steady body weight increase was hindered due to disease induction (DC, phenethyl isothiocyanate (PEITC)-diet, p = 0.00015 and 0.026 respectively) compared to mice that remained healthy throughout the experiment
It is noteworthy to mention that this partial recovery was achieved even when average food intake per mouse per day in the PEITC group (5.2 g/30 g B.W.) was slightly lower than in the other two groups (5.8 g/30 g B.W.), which could be due to difference in palatability, potentially arising from PEITC-enrichment
Summary
Colorectal cancer (CRC) is second among various cancers in terms of causing deaths in the United States, and it resulted in an estimated healthcare expenditure of $14 billion in 2014. Over 90% of localized CRC, when diagnosed early, would have a 5-year survival rate. Early detection is less common due to lack of compliance to screening regimens. For late diagnosed metastatic disease, survival rate drops to 8–12%. Cytotoxic chemotherapy is the only available treatment option for unresectable metastatic disease, to which the initial response frequently tapers off due to ensuing resistance within six months [1]. Due to this and other reasons, among cancer patients, the use of alternative treatments ranges between 30% and 75% worldwide and frequently includes dietary approaches [2]
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