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

Guoxiang Shen, Oo Khor Tin, Rong Hu, Siwang Yu, Sujit Nair, Chi Tang Ho, Bandaru S. Reddy, Mou Tuan Huang, Harold L. Newmark, Ah Ng Tony Kong

Research output: Contribution to journalArticlepeer-review

125 Scopus citations

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 Apc Min/+ 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.

Original languageEnglish (US)
Pages (from-to)9937-9944
Number of pages8
JournalCancer Research
Volume67
Issue number20
DOIs
StatePublished - Oct 15 2007

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Chemoprevention of familial adenomatous polyposis by natural dietary compounds sulforaphane and dibenzoylmethane alone and in combination in Apc <sup>Min/+</sup> mouse'. Together they form a unique fingerprint.

Cite this