[Chemopreventive effect of resveratrol to cancer].
OBJECTIVE
Carcinogenesis is a complex process and at least 3 stages, including initiation, promotion, and progression, have been proposed in the process of carcinogenesis. Resveratrol has attracted considerable attention due to its low toxicity and unique chemical structure. This study was designed to test chemopreventive effect of resveratrol to cancer using various animal models.


METHODS
Ames assay and micronucleus formation assay were used to test the antimutagenic activities of resveratrol. Croton oil-induced enhancement of ornithine decarboxylase (ODC) activities of dorsal epidermis cells in mouse and mouse ear edema model were used to investigate the anti-promotion effect of resveratrol. In addition,7,12-dimenthylbenz[a]anthracene (DMBA)/croton oil-induced mouse skin tumor model was used to evaluate chemopreventive effect of resveratrol to cancer in vivo.


RESULTS
In Ames test,100 microg/plate of resveratrol exhibited 42.2% of inhibition on the reversion of Salmonella typhimurium TA100 induced by methylmethansulfonate, and 200 microg/plate of resveratrol exhibited 91.8% of inhibition on the reversion induced by benzopyrene. Pretreatment of resveratrol prevented cyclophosphamide (CTX)-induced micronucleus formation of polychromatic erythrocytes of mice bone marrow in dose-dependent manner. Mice treated with 30 mg/kg of resveratrol for 6 days before croton oil exposure have palliative ear edema. Treatment of 180 mg/kg resveratrol for 3 days caused 69.3% decrease of ODC activities in croton oil-induced dorsal epidermis. It was shown that resveratrol could inhibit DMBA/croton oil-induced mouse skin papilloma, which includes prolonging the latent period of tumor occurrence, decreasing the incidence of papilloma, and reducing tumor number per mouse in dose-dependent manner.


CONCLUSIONS
Resveratrol has the ability of anti-mutation and anti-promotion of cancer and merit further studies as a potential cancer chemopreventive agent.
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
Zhao-Di
ZD
Fu
Yu
Y
Cao
Kai-Feng
KF
Wang
Shao-Feng
SF
Xu
Rui
R
Han
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D016587:Antimutagenic Agents / Q000633:toxicity; D003436:Croton Oil; D004427:Ear Diseases / Q000139:chemically induced / Q000517:prevention & control; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D004847:Epithelial Cells / Q000201:enzymology; D005260:Female; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009955:Ornithine Decarboxylase / Q000378:metabolism; D010212:Papilloma / Q000139:chemically induced / Q000517:prevention & control*; D000077185:Resveratrol; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013267:Stilbenes / Q000627:therapeutic use* / Q000633:toxicity
D016588:Anticarcinogenic Agents; D016587:Antimutagenic Agents; D013267:Stilbenes; D015127:9,10-Dimethyl-1,2-benzanthracene; D003436:Croton Oil; D009955:Ornithine Decarboxylase; D000077185:Resveratrol