title: Chemopreventive effects of β-ionone and geraniol during rat hepatocarcinogenesis promotion: distinct actions on cell proliferation, apoptosis, HMGCoA reductase, and RhoA.
abstract: Chemopreventive activities of the dietary isoprenoids β-ionone (βI) and geraniol (GOH) were evaluated during the promotion phase of hepatocarcinogenesis. Over 5 consecutive weeks, rats received daily 16 mg/100 g body weight (b.w.) of βI (βI group), 25 mg/100 g b.w. of GOH (GOH group), or only corn oil (CO group, controls). Compared to the CO group, the following was observed: only the βI group showed a decrease in the mean number of visible hepatocyte nodules (P<.05); βI and GOH groups had reduced mean number of persistent preneoplastic lesions (pPNLs) (P<.05), but no differences regarding number of remodeling PNL (rPNLs) were observed; only the βI group exhibited smaller rPNL size and percentage of liver sections occupied by pPNLs (P<.05), whereas the GOH group displayed a smaller percentage of liver sections occupied by rPNLs (P<.05); a trend was observed in the βI group, which showed reduced cell proliferation of pPNLs (P<.10), and the GOH group had increased apoptosis in pPNLs and rPNLs (P<.05); only the βI group displayed reduced total plasma cholesterol concentrations (P<.05) and increased hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase mRNA levels (P<.05); only the GOH group had lower hepatic membrane RhoA protein levels (P<.05); both the βI- and GOH-treated groups had higher hepatic concentrations of βI and GOH, respectively (P<.05). Given these data, βI and GOH show promising chemopreventive effects during promotion of hepatocarcinogenesis by acting through distinct mechanism of actions: βI may inhibit cell proliferation and modulate HMGCoA reductase, and GOH can induce apoptosis and inhibit RhoA activation.
authors.affiliation: Laboratory of Diet, Nutrition and Cancer, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, 05508-900, São Paulo, SP, Brazil.
authors.forename: Mônica Testoni
authors.initials: MT
authors.lastname: Cardozo
authors.forename: Aline
authors.initials: A
authors.lastname: de Conti
authors.forename: Thomas Prates
authors.initials: TP
authors.lastname: Ong
authors.forename: Clarissa
authors.initials: C
authors.lastname: Scolastici
authors.forename: Eduardo
authors.initials: E
authors.lastname: Purgatto
authors.forename: Maria Aderuza
authors.initials: MA
authors.lastname: Horst
authors.forename: Bruna Kempfer
authors.initials: BK
authors.lastname: Bassoli
authors.forename: Fernando Salvador
authors.initials: FS
authors.lastname: Moreno
mesh_terms: D000080462:Acyclic Monoterpenes; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism; D049109:Cell Proliferation; D018890:Chemoprevention; D002784:Cholesterol / Q000097:blood; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D045792:Norisoprenoids / Q000494:pharmacology*; D011230:Precancerous Conditions / Q000188:drug therapy / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013729:Terpenes / Q000494:pharmacology*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000080462:Acyclic Monoterpenes; D045792:Norisoprenoids; D013729:Terpenes; D002784:Cholesterol; C008157:beta-ionone; D006903:Hydroxymethylglutaryl CoA Reductases; D020742:rhoA GTP-Binding Protein; C007836:geraniol