title: 2,3',4,4',5'-Pentamethoxy-trans-stilbene, a resveratrol derivative, inhibits colitis-associated colorectal carcinogenesis in mice.
abstract: OBJECTIVE
  Resveratrol, a naturally occurring polyphenolic antioxidant, has been shown to exhibit chemoprophylactic effects on cancer development. Previously, we reported that 2,3',4,4',5'-pentamethoxy-trans-stilbene (PMS), a methoxylated resveratrol derivative, exerted a highly potent anti-proliferative effect on human colon cancer cells as compared with its parent compound. In the present study, the chemopreventive effect of PMS was evaluated in a mouse model of colitis-associated colon carcinogenesis.
  
  
  METHODS
  Seven-week-old Balb/c mice were injected i.p. with 10 mg.kg(-1) azoxymethane (AOM). After 1 week, 3% dextran sodium sulphate (DSS) was administered in the drinking water for 7 days followed by 14 days of tap water for recovery, and this cycle was repeated twice.
  
  
  RESULTS
  Intragastric administration of PMS (25, 50 mg.kg(-1) body weight) for 16 weeks significantly reduced the multiplicity of colonic neoplasms by 15% and 35% (P < 0.01) respectively. Moreover, PMS at 50 mg.kg(-1) inhibited colon cancer cell proliferation and promoted apoptosis. Such changes were accompanied by reduction of Akt (protein kinase B) phosphorylation, inactivation of beta-catenin and down-regulation of inducible nitric oxide synthase. In parallel, in vitro studies also demonstrated that PMS inhibited proliferation and induced apoptosis in the murine colon adenocarcinoma cell line Colon26 with concomitant inhibition of Akt phosphorylation and inactivation of beta-catenin.
  
  
  CONCLUSIONS
  PMS effectively suppressed colon carcinogenesis in an AOM/DSS animal model and may merit further clinical investigation as a chemoprophylactic agent against colitis-associated colon cancer in humans.
authors.affiliation: School of Biological Sciences, The University of Hong Kong, Hong Kong, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Li
authors.forename: William Ka Kei
authors.initials: WK
authors.lastname: Wu
authors.forename: Zhi Jie
authors.initials: ZJ
authors.lastname: Li
authors.forename: Kam Ming
authors.initials: KM
authors.lastname: Chan
authors.forename: Clover Ching Man
authors.initials: CC
authors.lastname: Wong
authors.forename: Cai Guo
authors.initials: CG
authors.lastname: Ye
authors.forename: Le
authors.initials: L
authors.lastname: Yu
authors.forename: Joseph Jao Yiu
authors.initials: JJ
authors.lastname: Sung
authors.forename: Chi Hin
authors.initials: CH
authors.lastname: Cho
authors.forename: Mingfu
authors.initials: M
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001397:Azoxymethane / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003092:Colitis / Q000150:complications*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D015179:Colorectal Neoplasms / Q000517:prevention & control*; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: C544677:2,3',4,4',5'-pentamethoxystilbene; D013267:Stilbenes; D016264:Dextran Sulfate; D001397:Azoxymethane