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Carcinogenesis Advance Access published online on May 4, 2006

Carcinogenesis, doi:10.1093/carcin/bgl049
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
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 *

1 Department of Pharmaceutics, Inje University, Gimhae, Gyeongnam, South Korea
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

* To whom correspondence should be addressed.
Ah-Ng Tony Kong, E-mail: KongT{at}rci.rutgers.edu


   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 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, {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 3-30 nmol/g are required to prevent, or retard adenoma formation in the gastrointestinal tract of ApcMin/+ mice.

Keywords: Sulforaphane; Cancer chemoprevention; ApcMin/+.
2These authors contributed equally to this work
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