Carcinogenesis Advance Access originally published online on May 4, 2006
Carcinogenesis 2006 27(10):2038-2046; doi:10.1093/carcin/bgl049
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Cancer chemoprevention of intestinal polyposis in ApcMin/+ mice by sulforaphane, a natural product derived from cruciferous vegetable
1 Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey Piscataway, NJ 08854, USA
2 Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey Piscataway, NJ 08854, USA
3 Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey Piscataway, NJ 08854, USA
4 Food Science Institute School of Food and Life Science, College of Biomedical Science & Engineering, Inje University, Gimhae, Gyeongnam South Korea
*To whom correspondence should be addressed.Email: KongT{at}rci.rutgers.edu
Sulforaphane (SFN) is an isothiocyanate that is present abundantly in widely consumed cruciferous vegetables and has a particularly high content in broccoli and cauliflower. It has been shown to be an effective inhibitor of some carcinogen-induced cancers in rodents. Here, we investigated the chemopreventive efficacy of SFN in the ApcMin/+ mouse model. ApcMin/+ mice were fed with diet supplemented with two different dose levels of SFN (300 and 600 p.p.m.) for 3 weeks. Our results clearly demonstrated that ApcMin/+ mice fed with SFN-supplemented diet developed significantly less and smaller polyps with higher apoptotic and lower proliferative indices in their small intestine, in a SFN dose-dependent manner. In addition, immunohistochemical (IHC) staining of the adenomas indicated that SFN significantly suppressed the expression of phosphorylated c-Jun N-terminal kinase (p-JNK), phosphorylated extracellular signal-regulated kinases (p-ERK) and phosphorylated-Akt (p-Akt), which were found to be highly expressed in the adenomas of ApcMin/+ mice. In contrast, expression of two important biomarkers of the Wnt signaling pathway, ß-catenin and cyclin-D1 was unaffected by SFN treatment. Measurement of SFN and its metabolite SFN–GSH in the small intestine using LC–MS indicates that the concentrations between 3 and 30 nmol/g are required to prevent, or retard adenoma formation in the gastrointestinal tract of ApcMin/+ mice.
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