A single dose of caffeic acid phenethyl ester prevents initiation in a medium-term rat hepatocarcinogenesis model.
OBJECTIVE
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 25th 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 25th d. We evaluated the expression of preneoplastic markers as gamma-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 25th d after CT CAPE reduced the observed increase of GGT+AHF by 84% and liver expression of ggt 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 5 microM CAPE concentration.


CONCLUSIONS
Our results demonstrated that CAPE possesses anti-genotoxic and antineoplastic capabilities, by an anti-oxidative and free-radical scavenging mechanism.
Carrasco-Legleu
Claudia-Esther
CE
Departamento de Biología Celular, Laboratorio 50, Centro de Investigación y de Estudios Avanzados del IPN (Cinvestav). Ave. IPN #2508. Col. San Pedro Zacatenco, C.P. 07360, México, D.F., México.
Sánchez-Pérez
Yesennia
Y
Márquez-Rosado
Lucrecia
L
Fattel-Fazenda
Samia
S
Arce-Popoca
Evelia
E
Hernández-García
Sergio
S
Villa-Treviño
Saúl
S
D015073:2-Acetylaminofluorene; D000818:Animals; D002109:Caffeic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D002273:Carcinogens; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003603:Cytotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D004052:Diethylnitrosamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D051549:Glutathione S-Transferase pi / Q000235:genetics / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D018384:Oxidative Stress / Q000187:drug effects; D010626:Phenylethyl Alcohol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D005723:gamma-Glutamyltransferase / Q000235:genetics / Q000378:metabolism
D002109:Caffeic Acids; D002273:Carcinogens; D003603:Cytotoxins; D016328:NF-kappa B; D012333:RNA, Messenger; D004052:Diethylnitrosamine; D015073:2-Acetylaminofluorene; D005723:gamma-Glutamyltransferase; D051549:Glutathione S-Transferase pi; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol