title: Chemopreventive effects of nobiletin and its colonic metabolites on colon carcinogenesis.
abstract: METHODS
  Nobiletin (NBT) is a major citrus flavonoid with various health benefits. Herein, we investigated the colon cancer chemopreventive effects of NBT and its colonic metabolites in a colitis-associated colon carcinogenesis mouse model as well as in human colon cancer cell models.
  
  
  RESULTS
  In azoxymethane/dextran sulfate sodium treated mice, oral administration of NBT effectively decreased both incidence and multiplicity of colonic tumors. NBT showed significant antiproliferative, proapoptotic, and anti-inflammatory effects in the mouse colon. HPLC analysis revealed that oral administration of NBT resulted in high levels of metabolites, i.e. 3'-demethylnobiletin (M1), 4'-demethylnobiletin (M2), and 3',4'-didemethylnobiletin (M3) in the colonic mucosa. In contrast, the colonic level of NBT was about 20-fold lower than the total colonic level of three metabolites. Cell culture studies demonstrated that the colonic metabolites of NBT significantly inhibited the growth of human colon cancer cells, caused cell-cycle arrest, induced apoptosis, and profoundly modulated signaling proteins related with cell proliferation and cell death. All of these effects were much stronger than those produced by NBT alone.
  
  
  CONCLUSIONS
  Our results demonstrated that oral administration of NBT significantly inhibited colitis-associated colon carcinogenesis in mice, and this chemopreventive effect was strongly associated with its colonic metabolites.
authors.affiliation: Department of Food Science, University of Massachusetts, Amherst, MA, USA.
authors.forename: Xian
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Food Science, University of Massachusetts, Amherst, MA, USA.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Song
authors.affiliation: Department of Food Science, University of Massachusetts, Amherst, MA, USA.
authors.forename: Minqi
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Food Science, University of Massachusetts, Amherst, MA, USA.|Institute of Agro-Products Processing Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, P. R. China.
authors.forename: Jinkai
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Food Science, University of Massachusetts, Amherst, MA, USA.
authors.forename: Zili
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Department of Food Science, University of Massachusetts, Amherst, MA, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Food Science, University of Massachusetts, Amherst, MA, USA.
authors.forename: Guodong
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Food Science, University of Massachusetts, Amherst, MA, USA.
authors.forename: Hang
authors.initials: H
authors.lastname: Xiao
mesh_terms: D000284:Administration, Oral; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003092:Colitis / Q000150:complications; D003110:Colonic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D047309:Flavones / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000209:etiology
chemical_list: C534647:3',4'-didemethylnobiletin; C515880:3'-demethylnobiletin; C515881:4'-demethylnobiletin; D016588:Anticarcinogenic Agents; D016207:Cytokines; D047309:Flavones; C008661:nobiletin
keywords: Chemoprevention; Colitis; Colon carcinogenesis; Metabolites; Nobiletin