Carcinogenesis Advance Access published online on May 4, 2006
Carcinogenesis, doi:10.1093/carcin/bgl049
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1 Department of Pharmaceutics, Inje University, Gimhae, Gyeongnam, South Korea
* To whom correspondence should be addressed. 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 2 different dose levels of SFN (300 ppm and 600 ppm) 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,
Received January 9, 2006
Revised March 23, 2006
Accepted March 31, 2006
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Cancer chemoprevention of intestinal polyposis in ApcMin/+ mice by sulforaphane, a natural product derived from cruciferous vegetable
Rong Hu 1 2,
Tin Oo Khor 1 2,
Guoxiang Shen 1,
Woo-Sik Jeong 2,
Vidya Hebbar 1,
Chi Chen 1,
Changjiang Xu 1,
Bandaru Reddy 3,
Kiran Chada 4,
and
Ah-Ng Tony Kong 1 *
2 Department of Pharmaceutics, Inje University, Gimhae, Gyeongnam, South Korea; Food Science Institute, School of Food & Life Science, College of Biomedical Science & Engineering, Inje University, Gimhae, Gyeongnam, South Korea
3 Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
4 Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, NJ
Ah-Ng Tony Kong, E-mail: KongT{at}rci.rutgers.edu
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Abstract
-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 3-30 nmol/g are required to prevent, or retard adenoma formation in the gastrointestinal tract of ApcMin/+ mice.
2These authors contributed equally to this work
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