title: β-ionone inhibits persistent preneoplastic lesions during the early promotion phase of rat hepatocarcinogenesis: TGF-α, NF-κB, and p53 as cellular targets.
abstract: Dietary isoprenic derivatives such as β-ionone (βI) are a promising class of chemopreventive agents. In this study, cellular aspects of βI protective activities during early hepatocarcinogenesis were evaluated. Male Wistar rats were submitted to "resistant hepatocyte" model and then received daily 16 mg/100 g body weight (b.w.) of βI (βI group) or only 0.25 mL/100 g b.w. of corn oil (vehicle, control group [CO]) during 4 wk, specifically during early promotion phase. Compared to controls, βI inhibited (P < 0.05) the development of persistent preneoplastic lesions (pPNL), considered to be potential hepatocellular carcinoma (HCC) progression sites, and increased remodeling PNL (rPNL) (P < 0.05) that tend to regress to a normal phenotype. Increased βI hepatic levels (P < 0.05), in the βI group, were associated with its chemopreventive actions. Compared to control rats, βI reduced the frequency of both pPNL and rPNL positive for tumor growth factor (TGF)-α (P < 0.05), reduced the frequency of pPNL stained for p65 (nuclear factor-kappaB; NF-κB) (P < 0.05), and reduced the frequency of pPNL positive for cytoplasmic p53 (P < 0.05). Our data demonstrated that βI targets TGF-α, NF-κB, and p53 in initial phases of hepatocarcinogenesis and specifically inhibits PNL with increased probability to progress to HCC. This isoprenoid may represent a chemopreventive agent of choice for HCC control.
authors.affiliation: a Laboratory of Diet, Nutrition and Cancer, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences , University of São Paulo , São Paulo , Brazil.
authors.forename: Clarissa
authors.initials: C
authors.lastname: Scolastici
authors.forename: Aline
authors.initials: A
authors.lastname: de Conti
authors.forename: Mônica Testoni
authors.initials: MT
authors.lastname: Cardozo
authors.forename: Thomas Prates
authors.initials: TP
authors.lastname: Ong
authors.forename: Eduardo
authors.initials: E
authors.lastname: Purgatto
authors.forename: Maria Aderuza
authors.initials: MA
authors.lastname: Horst
authors.forename: Renato
authors.initials: R
authors.lastname: Heidor
authors.forename: Kelly Silva
authors.initials: KS
authors.lastname: Furtado
authors.forename: Bruna Kempfer
authors.initials: BK
authors.lastname: Bassoli
authors.forename: Fernando Salvador
authors.initials: FS
authors.lastname: Moreno
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D018890:Chemoprevention; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D045792:Norisoprenoids / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016211:Transforming Growth Factor alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D016328:NF-kappa B; D045792:Norisoprenoids; D016211:Transforming Growth Factor alpha; D016159:Tumor Suppressor Protein p53; C008157:beta-ionone