title: The effect of caffeic acid phenethyl ester analogues in a modified resistant hepatocyte model.
abstract: We present a study of the chemoprotective effects of two caffeic acid phenethyl ester (CAPE)-related structures: LQM717 and LQM706. The modified resistant hepatocyte model in rats was used to study the chemoprevention of these CAPE analogues, which are inexpensive and easily obtained. In the liver cancer model used, we detected extensive necrosis and lipid peroxidation after 24 h, many altered hepatic foci, putatively preneoplastic lesions with γ-glutamyl transpeptidase staining after 30 days, and liver tumors at 12 months. We tested the effect of the CAPE analogues on necrosis, lipid peroxidation, proliferation, p65 activation, altered hepatic foci, and tumors. Both compounds exerted protective effects on lipid peroxidation, necrosis, cell proliferation, p65 activation, and preneoplastic lesions. Rats under a carcinogenic protocol showed a 52, 71.74, and 51.6% decrease in the number of preneoplastic nodules when pretreated with CAPE, LQM706, and LQM717, respectively. At 12 months after carcinogenic treatment, eight of eight rats developed liver cancer, whereas in the group of rats that received pretreatment with CAPE, LQM706, or LQM717, 62.5, 83.3, or 42.85%, respectively, had tumors. In conclusion, LQM717 has the potential to enhance chemoprotection activity much better than CAPE by markedly reducing the formation of liver cancers in this model, and this is a compound that is easy to obtain.
authors: Department of Cell Biology, Center for Research and Advanced Studies, National Polytechnic Institute, National Autonomous University of México, Cuautitlán Izcalli, State of México, México D.F., México.
authors: José R
authors: JR
authors: Macías-Pérez
authors: Olga
authors: O
authors: Beltrán-Ramírez
authors: Verónica R
authors: VR
authors: Vásquez-Garzón
authors: Martha E
authors: ME
authors: Salcido-Neyoy
authors: Pablo A
authors: PA
authors: Martínez-Soriano
authors: Mónica B
authors: MB
authors: Ruiz-Sánchez
authors: Enrique
authors: E
authors: Angeles
authors: Saúl
authors: S
authors: Villa-Treviño
mesh_terms: D015073:2-Acetylaminofluorene; D000083:Acetanilides / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D016588:Anticarcinogenic Agents / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D002109:Caffeic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D002273:Carcinogens; D002455:Cell Division / Q000187:drug effects; D002934:Cinnamates / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D004052:Diethylnitrosamine; D004353:Drug Evaluation, Preclinical; D004351:Drug Resistance; D051549:Glutathione S-Transferase pi / Q000032:analysis; D006498:Hepatectomy / Q000009:adverse effects; D022781:Hepatocytes / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D019394:Ki-67 Antigen / Q000032:analysis; D015227:Lipid Peroxidation / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D015394:Molecular Structure; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D011230:Precancerous Conditions / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000083:Acetanilides; D016588:Anticarcinogenic Agents; D000975:Antioxidants; D002109:Caffeic Acids; D002273:Carcinogens; D002934:Cinnamates; D019394:Ki-67 Antigen; C582799:LQM706; C582798:LQM717; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D004052:Diethylnitrosamine; D015073:2-Acetylaminofluorene; D051549:Glutathione S-Transferase pi; C496558:Gstp1 protein, rat; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol