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: Rong Hu, Tin Oo Khor, Guoxiang Shen, Woo-Sik Jeong, Vidya Hebbar, Chi Chen, Changjiang Xu, Bandaru Reddy, Kiran Chada, Ah-Ng Tony Kong
• Journal: Carcinogenesis (Carcinogenesis) Vol. 27 Issue 10 Pg. 2038-46 (Oct 2006) ISSN: 0143-3334 [Print] England
• PMID: 16675473 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Anticarcinogenic Agents
• Codon, Nonsense
• Isothiocyanates
• Sulfoxides
• Thiocyanates
• Extracellular Signal-Regulated MAP Kinases
• sulforaphane

Topics

• Adenoma (prevention & control)
• Animals
• Anticarcinogenic Agents (administration & dosage)
• Cell Proliferation (drug effects)
• Codon, Nonsense
• Colorectal Neoplasms (prevention & control)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Genes, APC
• Intestinal Polyps (drug therapy)
• Isothiocyanates
• MAP Kinase Signaling System (drug effects)
• Mice
• Sulfoxides
• Thiocyanates (administration & dosage, pharmacokinetics)