Cancer chemoprevention of intestinal polyposis in = ApcMin/+ mice by sulforaphane, a natural product derived from = cruciferous vegetable -- Hu et al., 10.1093/carcin/bgl049 -- = Carcinogenesis

Carcinogenesis Advance Access published online on = May 4,=20 2006
Carcinogenesis, = doi:10.1093/carcin/bgl049=20

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	Articles by Hu, R.
	Articles by Kong, A.-N. T. =

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	Articles by Hu, R.
	Articles by Kong, A.-N. T.=20 =

=A9 The Author 2006. Published by Oxford = University Press.=20 All rights reserved. For permissions, please email:=20 journals.permissions@oxfordjournals.org
Received=20 January 9, 2006
Revised March 23, = 2006
Accepted March 31, 2006

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION=20

Cancer chemoprevention of intestinal polyposis in ApcMin/+ mice by=20 sulforaphane, a natural product derived from cruciferous vegetable=20

Rong Hu ¹ ², Tin Oo Khor ¹ = ², Guoxiang Shen ¹, Woo-Sik Jeong ², = Vidya=20 Hebbar ¹, Chi Chen ¹, Changjiang Xu ¹, = Bandaru=20 Reddy ³, Kiran Chada ⁴, and Ah-Ng Tony = Kong=20 ¹ ^*

¹ Department of Pharmaceutics, Inje = University,=20 Gimhae, Gyeongnam, South Korea
² Department of = Pharmaceutics, Inje=20 University, Gimhae, Gyeongnam, South Korea; Food Science Institute, = School of=20 Food & Life Science, College of Biomedical Science & = Engineering, Inje=20 University, Gimhae, Gyeongnam, South Korea
³ Department of = Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State = University=20 of New Jersey, Piscataway, NJ 08854, USA
⁴ Department of=20 Biochemistry, Robert Wood Johnson Medical School, University of Medicine = and=20 Dentistry of New Jersey, Piscataway, NJ

^* To whom correspondence should be=20 addressed.
Ah-Ng Tony Kong,=20 E-mail: KongT{at}rci.rutgers.edu

3D" Abstract

	Abstract

Sulforaphane (SFN) is an isothiocyanate that is present = abundantly⁼²⁰in widely consumed cruciferous vegetables and has a = particularly⁼²⁰high content in broccoli and cauliflower. It has been shown⁼to=20 be an effective inhibitor of some carcinogen-induced cancers⁼in=20 rodents. Here, we investigated the chemopreventive efficacy⁼of SFN in=20 the ApcMin/+ mouse model. ApcMin/+ mice were fed withdiet=20 supplemented with 2 different dose levels of SFN (300 ppmand = 600=20 ppm) for 3-weeks. Our results clearly demonstrated that⁼ApcMin/+ mice=20 fed with SFN-supplemented diet developed significantlyless = and=20 smaller polyps with higher apoptotic and lower proliferative⁼indices=20 in their small intestine, in a SFN dose-dependent manner.In=20 addition, immunohistochemical (IHC) staining of the adenomas⁼²⁰indicated that SFN significantly suppressed the expression of⁼phosphorylated-c-Jun-N-terminal kinase (p-JNK),=20 phosphorylated-extracellularsignal-regulated kinases (p-ERK) = and=20 phosphorylated-Akt (p-Akt),which were found to be highly = expressed=20 in the adenomas of ApcMin/+mice. In contrast, expression of = two=20 important biomarkers ofthe Wnt signaling pathway, $3D{beta}=20$ -catenin and = cyclin-D1 was=20 unaffectedby SFN treatment. Measurement of SFN and its = metabolite=20 SFN-GSHin the small intestine using LC-MS indicates that the = concentrationsbetween 3-30 nmol/g are required to prevent, = or retard=20 adenomaformation in the gastrointestinal tract of ApcMin/+=20 mice.

Keywords: Sulforaphane; Cancer = chemoprevention;=20 ApcMin/+.=20

²These authors contributed equally to this work