Chemopreventive effect of trans-resveratrol--a phytoalexin against colonic aberrant crypt foci and cell proliferation in 1,2-dimethylhydrazine induced colon carcinogenesis.
Prevention of cancer remains a primary need and new chemopreventive agents must be developed for this purpose. Towards this goal, a chemoprevention study was conducted to evaluate the activity of resveratrol (Res), a phytoalexin, as an inhibitor of colon carcinogenesis. Wistar male rats were divided into six groups, group 1 were control rats, group 2 were control rats that received Res (8 mg/kg body wt p.o. everyday), rats in groups 3-6 were treated weekly with 1,2-dimethylhydrazine (DMH, 20 mg/kg body wt, s.c. x 15 times). In addition, groups 4, 5 and 6 received Res as in group 2. Modifying effects were assessed using aberrant crypt foci (ACF) and the extent of histopathological lesions as end point markers. At the end of 30 weeks, Res markedly reduced tumor incidence, the degree of histological lesions and also the size of tumors significantly (P < 0.05) as compared with the rats treated with unsupplemented DMH. The number of ACF consisting of more than six aberrant crypts per rat was observed in group 6 (6.2 +/- 1.4), group 5 (7.7 +/- 1.0) and group 4 (8.2 +/- 1.4) which were significantly lower than that of group 3 (22.3 +/- 2.4) (P < 0.05). The most pronounced inhibition of ACF development was noted in rats fed Res for the entire period and also during the post-initiation period. Also, Res administration lowered the number of argyrophilic nucleolar organizing region-associated proteins (AgNORs) per nucleus in non-lesional colonic crypts, which reflects the cell proliferation activity. Oxidative imbalance in DMH-treatment was significantly (P < 0.01) modulated on Res supplementation as indicated by optimal concentration of thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH). The results of our study suggest Res to be an effective chemopreventive agent, which suppresses DMH-induced colon carcinogenesis at various stages.
Sengottuvelan
Murugan
M
Department of Biochemistry and Biotechnology, Faculty of Science, Rajah Muthiah Medical College, Annamalai University, Annamalainagar-608 002, Tamilnadu, India.
Viswanathan
Periaswamy
P
Nalini
Namasivayam
N
D019813:1,2-Dimethylhydrazine / Q000633:toxicity*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D034961:Antigens, Nuclear / Q000494:pharmacology; D002273:Carcinogens; D049109:Cell Proliferation; D003106:Colon / Q000473:pathology; D003110:Colonic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D009687:Nuclear Proteins / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D012717:Sesquiterpenes; D013267:Stilbenes / Q000494:pharmacology*; D013729:Terpenes; D017392:Thiobarbituric Acid Reactive Substances; D000094162:Phytoalexins
D016588:Anticarcinogenic Agents; D034961:Antigens, Nuclear; D002273:Carcinogens; D004791:Enzyme Inhibitors; D009687:Nuclear Proteins; D010936:Plant Extracts; D012717:Sesquiterpenes; D013267:Stilbenes; D013729:Terpenes; D017392:Thiobarbituric Acid Reactive Substances; C051963:nucleolar organizer region associated proteins; D019813:1,2-Dimethylhydrazine; D000077185:Resveratrol; D000094162:Phytoalexins