title: Evidence that the anticarcinogenic effect of caffeic acid phenethyl ester in the resistant hepatocyte model involves modifications of cytochrome P450.
abstract: Caffeic acid phenethyl ester (CAPE), a natural component of propolis, shows anticarcinogenic properties in the modified resistant hepatocyte model when administered before initiation or promotion of hepatocarcinogenesis process; however, information about the mechanism underlying this chemoprotection is limited. The aim of this work was to characterize the effect of CAPE on cytochrome P450 (CYP), which is involved in diethylnitrosamine (DEN) metabolism during the initiation stage of chemical hepatocarcinogenesis. Male Fischer-344 rats were treated as in the modified resistant hepatocyte model. Liver samples were obtained at four different times: at 12 h after pretreatment with CAPE and at 12 and 24 h and 25 days after DEN administration. Liver damage was determined by histology with hematoxylin and eosin, measurement of total CYP levels and enzyme activity, and gamma-glutamyl transpeptidase-positive (GGT+) staining of hepatocyte foci. CAPE administration prevented DEN-induced necrosis at 24 h. It also decreased O-dealkylation of 7-ethoxy-resorufin (EROD), O-dealkylation of 7-methoxyresorufin (MROD), and 7-pentoxy-resorufin activities at 12 h after its administration and EROD and MROD activities at 12 h after administration of DEN. CAPE treatment decreased GGT+ foci by 59% on day 25. Our results suggest that CAPE modifies the enzymatic activity of CYP isoforms involved in the activation of DEN, such as CYP1A1/2 and CYP2B1/2. These findings describe an alternative mechanism for understanding the ability of CAPE to protect against chemical hepatocarcinogenesis.
authors.affiliation: Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), Avenida IPN No. 2508 Colonia San Pedro Zacatenco, México 14, DF, CP 07360, México.
authors.forename: Olga
authors.initials: O
authors.lastname: Beltrán-Ramírez
authors.forename: Leticia
authors.initials: L
authors.lastname: Alemán-Lazarini
authors.forename: Martha
authors.initials: M
authors.lastname: Salcido-Neyoy
authors.forename: Sergio
authors.initials: S
authors.lastname: Hernández-García
authors.forename: Samia
authors.initials: S
authors.lastname: Fattel-Fazenda
authors.forename: Evelia
authors.initials: E
authors.lastname: Arce-Popoca
authors.forename: Jaime
authors.initials: J
authors.lastname: Arellanes-Robledo
authors.forename: Rebeca
authors.initials: R
authors.lastname: García-Román
authors.forename: Patricia
authors.initials: P
authors.lastname: Vázquez-Vázquez
authors.forename: Adolfo
authors.initials: A
authors.lastname: Sierra-Santoyo
authors.forename: Saúl
authors.initials: S
authors.lastname: Villa-Treviño
mesh_terms: D015073:2-Acetylaminofluorene; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002109:Caffeic Acids / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004052:Diethylnitrosamine; D022781:Hepatocytes; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D002109:Caffeic Acids; D004052:Diethylnitrosamine; D003577:Cytochrome P-450 Enzyme System; D015073:2-Acetylaminofluorene; D005723:gamma-Glutamyltransferase; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol