2,3',4,4',5'-Pentamethoxy-trans-stilbene, a resveratrol derivative, inhibits colitis-associated colorectal carcinogenesis in mice.
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.
Li
Haitao
H
School of Biological Sciences, The University of Hong Kong, Hong Kong, China.
Wu
William Ka Kei
WK
Li
Zhi Jie
ZJ
Chan
Kam Ming
KM
Wong
Clover Ching Man
CC
Ye
Cai Guo
CG
Yu
Le
L
Sung
Joseph Jao Yiu
JJ
Cho
Chi Hin
CH
Wang
Mingfu
M
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*
C544677:2,3',4,4',5'-pentamethoxystilbene; D013267:Stilbenes; D016264:Dextran Sulfate; D001397:Azoxymethane