title: Identification of pinostilbene as a major colonic metabolite of pterostilbene and its inhibitory effects on colon cancer cells.
abstract: Pterostilbene (PTE) is a resveratrol derivative mainly found in blueberries, and it has been shown to inhibit colon carcinogenesis in multiple animal models. To shed light on the mechanism of PTE in inhibiting colon carcinogenesis, we investigated the PTE metabolites in the mouse colon and in the human colon cancer cells.
  
  
  
  CD-1 mice were fed PTE-containing diet for 3 weeks, and colonic content and colonic mucosa were collected and subjected to LC-MS analysis. Pinostilbene (PIN) was identified as a major metabolite of PTE in the mouse colon. Importantly, the level of PIN was found to be approximately equivalent to that of PTE in the colonic mucosa. PIN significantly inhibited the growth of human colon cancer cells, i.e., HCT116 and HT29. These inhibitory effects were similar to those produced by PTE. Moreover, under physiologically relevant conditions, 20 and 40 μM of PIN caused cell cycle arrest at S phase and induced apoptosis in colon cancer cells. These effects were associated with profound modulation of signaling proteins related with cell proliferation and programmed cell death.
  
  
  
  Our results demonstrated that PIN is a major metabolite of PTE in the colon of mice fed with PTE, and PIN may play important roles in the anti-colon cancer effects elicited by orally administered PTE.
authors.affiliation: School of Pharmacy, Ocean University of China, Qingdao, P. R. China.|Department of Food Science, University of Massachusetts, Amherst, MA, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
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: Xiaokun
authors.initials: X
authors.lastname: Cai
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.|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: Che
authors.initials: C
authors.lastname: Pan
authors.affiliation: School of Pharmacy, Ocean University of China, Qingdao, P. R. China.|Department of Food Science, University of Massachusetts, Amherst, MA, USA.
authors.forename: Peiju
authors.initials: P
authors.lastname: Qiu
authors.affiliation: School of Pharmacy, Ocean University of China, Qingdao, P. R. China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, Hunan, P. R. China.
authors.forename: Shuangde
authors.initials: S
authors.lastname: Zhou
authors.affiliation: College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, Hunan, P. R. China.
authors.forename: Zhonghai
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Department of Food Science, University of Massachusetts, Amherst, MA, USA. hangxiao@foodsci.umass.edu.|College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, Hunan, P. R. China. hangxiao@foodsci.umass.edu.
authors.forename: Hang
authors.initials: H
authors.lastname: Xiao
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045325:HCT116 Cells; D006801:Humans; D008658:Inactivation, Metabolic; D008297:Male; D008815:Mice, Inbred Strains; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D013267:Stilbenes / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*
chemical_list: D013267:Stilbenes; C522997:pinostilbene; C107773:pterostilbene
keywords: Apoptosis; Cell cycle arrest; Colon cancer; Metabolite; Pinostilbene; Pterostilbene