title: Orally administered lycopene attenuates diethylnitrosamine-induced hepatocarcinogenesis in rats by modulating Nrf-2/HO-1 and Akt/mTOR pathways.
abstract: Hepatocarcinogenesis is one of the most prevalent and lethal cancers. We studied the mechanisms underlying the inhibition of diethylnitrosamine (DEN)-induced hepatocarcinogenesis by lycopene in rats. Hepatocarcinogenesis was induced by an intraperitoneal injection of DEN followed by promotion with phenobarbital for 24 successive wk. The rats were given lycopene (20 mg/kg body weight) 3 times a week orally for 4 wk prior to initiation, and the treatment was continued for 24 consecutive wk. Lycopene reduced incidence, number, size, and volume of hepatic nodules. Serum alanine transaminase, aspartate aminotransferase, total bilirubin, and malondialdehyde (MDA) considerably increased and hepatic antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase) and glutathione decreased in DEN-treated rats when compared with the control group. Lycopene significantly reversed these biochemical changes and increased the expression of NF-E-2-related factor-2)/heme oxygenase-1, and it decreased NF-κB/cyclooxygenase-2, inhibiting the inflammatory cascade and activating antioxidant signaling (P < 0.05). Lycopene also decreased DEN-induced increases in phosphorylated mammalian target of rapamycin (p-mTOR), phosphorylated p70 ribosomal protein S6 kinase 1, phosphorylated 4E-binding protein 1, and protein kinase B (P < 0.05). Lycopene is an active chemopreventive agent that offers protection against DEN-induced hepatocarcinogenesis by inhibiting NF-κB and mTOR pathways.
authors.affiliation: a Department of Animal Nutrition, Faculty of Veterinary Science , Firat University , Elazig , Turkey.
authors.forename: Kazim
authors.initials: K
authors.lastname: Sahin
authors.forename: Cemal
authors.initials: C
authors.lastname: Orhan
authors.forename: Mehmet
authors.initials: M
authors.lastname: Tuzcu
authors.forename: Nurhan
authors.initials: N
authors.lastname: Sahin
authors.forename: Shakir
authors.initials: S
authors.lastname: Ali
authors.forename: Ibrahim H
authors.initials: IH
authors.lastname: Bahcecioglu
authors.forename: Osman
authors.initials: O
authors.lastname: Guler
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Ozercan
authors.forename: Necip
authors.initials: N
authors.lastname: Ilhan
authors.forename: Omer
authors.initials: O
authors.lastname: Kucuk
mesh_terms: D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002338:Carotenoids / Q000494:pharmacology*; D002374:Catalase / Q000097:blood; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004052:Diethylnitrosamine / Q000009:adverse effects; D005978:Glutathione / Q000097:blood; D005979:Glutathione Peroxidase / Q000097:blood; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000139:chemically induced / Q000188:drug therapy*; D000077276:Lycopene; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000097:blood; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495637:Nfe2l2 protein, rat; D002338:Carotenoids; D004052:Diethylnitrosamine; D008315:Malondialdehyde; D002374:Catalase; D005979:Glutathione Peroxidase; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C546845:mTOR protein, rat; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D005978:Glutathione; D001663:Bilirubin; D000077276:Lycopene