A single dose of caffeic acid phenethyl ester prevents initiation in a medium-term rat hepatocarcinogenesis model

• Published in: World journal of gastroenterology : WJG Vol. 12; no. 42; pp. 6779 - 6785
• Main Author: Claudia Esther Carrasco-Legleu Yesennia Sánchez-Pérez Lucrecia Márquez-Rosado Samia Fattel-Fazenda Evelia Arce-Popoca Sergio Hernández-García Saúl Villa-Trevino
• Format: Journal Article
• Language: English
• Published: United States Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del IPN (Cinvestav). Ave. IPN #2508. Col. San Pedro Zacatenco, C.P. 07360, México, D.F., México%Instituto Nacional de Cancerología,San Femando No. 22, C.P. 14080, México, D.F., México 14.11.2006; Baishideng Publishing Group Co., Limited
• Subjects: 2-Acetylaminofluorene; Animals; Caffeic Acids - administration & dosage; Caffeic Acids - pharmacology; Carcinogens; Cell Proliferation - drug effects; Cell Transformation, Neoplastic - chemically induced; Cell Transformation, Neoplastic - drug effects; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; Cytotoxins - administration & dosage; Cytotoxins - pharmacology; Diethylnitrosamine - metabolism; Dose-Response Relationship, Drug; gamma-Glutamyltransferase - genetics; gamma-Glutamyltransferase - metabolism; Gene Expression Regulation, Enzymologic - drug effects; Glutathione S-Transferase pi - genetics; Glutathione S-Transferase pi - metabolism; Lipid Peroxidation - drug effects; Liver Cancer; Liver Neoplasms, Experimental - chemically induced; Liver Neoplasms, Experimental - metabolism; Liver Neoplasms, Experimental - pathology; Liver Neoplasms, Experimental - prevention & control; Male; NF-kappa B - antagonists & inhibitors; Oxidative Stress - drug effects; Phenylethyl Alcohol - administration & dosage; Phenylethyl Alcohol - analogs & derivatives; Phenylethyl Alcohol - pharmacology; Rats; Rats, Wistar; RNA, Messenger - genetics; RNA, Messenger - metabolism; 咖啡酸; 肝细胞癌; 苯乙基; Hepatocarcinogenesis; Antioxidant; Initiation; Caffeic acid phenethyl ester
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v12.i42.6779

AIM： To study of the effect of caffeic acid phenethyl ester （CAPE） on the initiation period in a medium-term assay of hepatocarcinogenesis. METHODS： Male Wistar rats were subjected to a carcinogenic treatment （CT） and sacrificed at 25^th d; altered hepatic foci （AHF） were generated efficiently. To a second group of rats a single 20 mg/kg doses of CAPE was given 12 h before initiation with CT and were sacrificed at 25^th d. We evaluated the expression of preneoplastic markers as Y-glutamyltranspeptidase （GGT） and glutathione S-transferase type pi protein （GSTp） by histochemistry, RT-PCR and Western blot analyses, respectively. We measured thiobarbituric acid reactive substances （TBARS） in homogenates of liver and used Unscheduled DNA Synthesis （UDS） assay by incorporation of [^3H] thymidine （^3HdT） in primary hepatocyte cultures （PHC）. RESULTS： At 25^th d after CT CAPE reduced the observed increase of GGT^＋AHF by 84% and liver expression ofggt mRNA by 100%. In case of the GSTp protein, the level was reduced by 90%. As indicative of oxidative stress generated by diethylnitrosamine （DEN） 12 h after its administration, we detected a 68% increase of TBARS. When CAPE was administered before DEN, it completely protected from liver TBARS induction. To have an indication of the sole effect of CAPE on initiation, two carcinogens were tested in a UDS assay in PHC, we used methyl-n-nitrosoguanidine as a direct carcinogen and DEN, as indirect carcinogen. In this assay, genotoxic damage caused by carcinogens was abolished at 5μM CAPE concentration. CONCLUSION： Our results demonstrated that CAPE possesses anti-genotoxic and antineoplastic capabilities, by an anti-oxidative and free-radical scavenging mechanism.