Chemopreventive effects of β-ionone and geraniol during rat hepatocarcinogenesis promotion: distinct actions on cell proliferation, apoptosis, HMGCoA reductase, and RhoA.
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.
Cardozo
Mônica Testoni
MT
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.
de Conti
Aline
A
Ong
Thomas Prates
TP
Scolastici
Clarissa
C
Purgatto
Eduardo
E
Horst
Maria Aderuza
MA
Bassoli
Bruna Kempfer
BK
Moreno
Fernando Salvador
FS
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*
D000080462:Acyclic Monoterpenes; D045792:Norisoprenoids; D013729:Terpenes; D002784:Cholesterol; C008157:beta-ionone; D006903:Hydroxymethylglutaryl CoA Reductases; D020742:rhoA GTP-Binding Protein; C007836:geraniol