Abstract

anti-inflammatory effects by activating nrf2-mediated NF-κB inactivation (Oncogene, 24:4486, 2005). SFN induces apoptosis of cancer cells In Vitro (JBC 280:19911,2005). Thus, daily intake of dietary SFN may be safe and useful approach to afford long term chemoprotection against inflammation-related cancers. Based on these backgrounds, we hypothesized if SFN could strengthen the chemoprotective effects of NSAIDs against colon cancer, thereby enables to reduce the dose and the duration of NSAIDs use in cancer chemoprevention. In the present study, we examined if SFN modulates NSAIDs-induced chemoprotection against colitis-associated colon tumor in mice. Methods: C57BL/6 female mice were treated with 10 mg/kg azoxymethane (AOM), followed by 6 days treatment with 2% dextran sodium sulfate (DSS), as previously described. These mice were divided into the following 4 groups. Control Group: No further treatment. Sulindac (SLD) Group: Treated with SLD alone. SFN Group: Treated with SFN alone. SFN + SLD Group: Treated with both SFN and SLD. SLD, 160 ppm/day, was orally administrated during the first 8 weeks after the DSS treatment. SFN, 2.5 mmol/day, was orally administrated as broccoli sprout juice throughout the experimental period. Mice were sacrificed at 8 and 16 wks after the DSS treatment. Degree of colitis, size and number of colon tumors were quantitatively evaluated. Apoptosis and cell proliferation were assessed by immunostaining of themucosal preparations with TUNEL and PCNA, respectively. Degree of mucosal inflammation was assessed by histology and by measuring mucosal levels of TNF-α and IL-1β mRNA. Results: 1. SLD alone did not affect DSS-induced inflammation, but increased TUNEL-positive cells, decreased PCNA postive cells, and inhibited tumor formation in colonic mucosa. 2. SFN alone decreased expression of TNF-α and IL-1β, mitigated DSS-induced colitis, and slightly attenuated tumor formation. 3. SFN + SLD attenuated DSS-induced colitis, and markedly suppressed colon tumor formation. Conclusions: Daily intake of SFN-rich broccoli sprouts improves DSS-induced colitis and enhances SLD-induced chemoprevention against colon tumor in AOM +DSS treated mice. Our data suggest that a diet rich in SFN in combination with minimal dose of NSAID may be useful in chemoprevention against colitis-associated colon cancer.

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