title: Cancer chemoprevention of intestinal polyposis in ApcMin/+ mice by sulforaphane, a natural product derived from cruciferous vegetable.
abstract: 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, beta-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.
authors: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors: Rong
authors: R
authors: Hu
authors: Tin Oo
authors: TO
authors: Khor
authors: Guoxiang
authors: G
authors: Shen
authors: Woo-Sik
authors: WS
authors: Jeong
authors: Vidya
authors: V
authors: Hebbar
authors: Chi
authors: C
authors: Chen
authors: Changjiang
authors: C
authors: Xu
authors: Bandaru
authors: B
authors: Reddy
authors: Kiran
authors: K
authors: Chada
authors: Ah-Ng Tony
authors: AN
authors: Kong