Chemoprevention of familial adenomatous polyposis by natural dietary compounds sulforaphane and dibenzoylmethane alone and in combination in ApcMin/+ mouse.

Abstract

Cancer chemopreventive agent sulforaphane (SFN) and dibenzoylmethane (DBM) showed antitumorigenesis effects in several rodent carcinogenesis models. In this study, we investigated the cancer chemopreventive effects and the underlying molecular mechanisms of dietary administration of SFN and DBM alone or in combination in the ApcMin/+ mice model. Male ApcMin/+ mice (12 per group) at age of 5 weeks were given control AIN-76A diet, diets containing 600 ppm SFN and 1.0% DBM, or a combination of 300 ppm SFN and 0.5% DBM for 10 weeks. Mice were then sacrificed, and tumor numbers and size were examined. Microarray analysis, Western blotting, ELISA, and immunohistochemical staining were done to investigate the underlying molecular mechanisms of cancer chemopreventive effects of SFN and DBM. Dietary administrations of SFN and DBM alone or in combination significantly inhibited the development of intestinal adenomas by 48% (P=0.002), 50% (P=0.001), and 57% (P<0.001), respectively. Dietary administration of 600 ppm SFN and 1.0% DBM also reduced colon tumor numbers by 80% (P=0.016) and 60% (P=0.103), respectively, whereas the combination of SFN and DBM treatment blocked the colon tumor development (P=0.002). Both SFN and DBM treatments resulted in decreased levels of prostaglandin E2 or leukotriene B4 in intestinal polyps or apparently normal mucosa. Treatments also led to the inhibition of cell survival and growth-related signaling pathways (such as Akt and extracellular signal-regulated kinase) or biomarkers (such as cyclooxygenase-2, proliferating cell nuclear antigen, cleaved caspases, cyclin D1, and p21). In conclusion, our results showed that both SFN and DBM alone as well as their combination are potent natural dietary compounds for chemoprevention of gastrointestinal cancers.

• Authors: Guoxiang Shen, Tin Oo Khor, Rong Hu, Siwang Yu, Sujit Nair, Chi-Tang Ho, Bandaru S Reddy, Mou-Tuan Huang, Harold L Newmark, Ah-Ng Tony Kong
• Journal: Cancer research (Cancer Res) Vol. 67 Issue 20 Pg. 9937-44 (Oct 15 2007) ISSN: 0008-5472 [Print] United States
• PMID: 17942926 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Anticarcinogenic Agents
• Cell Cycle Proteins
• Chalcones
• Isothiocyanates
• Sulfoxides
• Thiocyanates
• Arachidonic Acid
• dibenzoylmethane
• Proto-Oncogene Proteins c-akt
• Mitogen-Activated Protein Kinases
• sulforaphane

Topics

• Adenomatous Polyposis Coli (genetics, metabolism, prevention & control)
• Animals
• Anticarcinogenic Agents (administration & dosage, pharmacokinetics, pharmacology)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, pharmacology)
• Apoptosis (drug effects)
• Arachidonic Acid (metabolism)
• Body Weight (drug effects)
• Cell Cycle Proteins (biosynthesis)
• Chalcones (administration & dosage, pharmacokinetics, pharmacology)
• Diet
• Gene Expression Profiling
• Intestine, Small (metabolism)
• Isothiocyanates
• Male
• Mice
• Mitogen-Activated Protein Kinases (metabolism)
• Phosphorylation (drug effects)
• Polymerase Chain Reaction
• Proto-Oncogene Proteins c-akt (metabolism)
• Sulfoxides
• Thiocyanates (administration & dosage, pharmacokinetics, pharmacology)