Farnesol and geraniol chemopreventive activities during the initial phases of hepatocarcinogenesis involve similar actions on cell proliferation and DNA damage, but distinct actions on apoptosis, plasma cholesterol and HMGCoA reductase.
Chemopreventive activities of farnesol (FOH) and geraniol (GOH) were evaluated during the initial phases of hepatocarcinogenesis. Rats received during eight consecutive weeks 25 mg/100 g body weight FOH (FOH group) or GOH (GOH group), or only corn oil (CO group, controls). Incidence (%) and mean number of visible hepatocyte nodules/animal were inhibited in FOH group (13% and 4 +/- 1; P < 0.05), but not in GOH group (42% and 18 +/- 17, P > 0.05), compared to CO group (100% and 42 +/- 17). Mean area (mm2) and % liver section area occupied by total hepatic placental glutathione S-transferase positive preneoplastic lesions (PNLs) were reduced in FOH group (0.09 +/- 0.06; 2.8 +/- 1.3; P < 0.05) compared to CO group (0.18 +/- 0.12; 10.0 +/- 2.8), while in GOH group only the mean area of these PNL was reduced (0.11 +/- 0.09; P < 0.05), but not the % liver section area occupied by them (5.1 +/- 1.1; P > 0.05). Compared to CO group, FOH and GOH groups showed reduced (P < 0.05) PNL cell proliferation and DNA damage, but only GOH group showed increased PNL apoptosis (P < 0.05). FOH group, but not GOH group, presented reduced (P < 0.05) total plasma cholesterol levels and increased (P < 0.05) hepatic levels of 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase mRNA, compared to CO group. No differences (P > 0.05) were observed between CO, FOH and GOH regarding hepatic levels of farnesoid X activated receptor (FXR) protein. Results indicate that FOH and GOH could represent promising chemopreventive agents against hepatocarcinogenesis. Inhibition of cell proliferation and DNA damage relate to both isoprenoids' anticarcinogenic actions while induction of apoptosis specifically relates to GOH protective actions. Inhibition of HMGCoA reductase activity could be associated with FOH, but not GOH anticarcinogenic actions. FXR does not seem to be involved in the isoprenoids' chemopreventive activities.
Ong
Thomas Prates
TP
Laboratory of Diet, Nutrition and Cancer, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Heidor
Renato
R
de Conti
Aline
A
Dagli
Maria Lúcia Zaidan
ML
Moreno
Fernando Salvador
FS
D000080462:Acyclic Monoterpenes; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis; D049109:Cell Proliferation; D002784:Cholesterol / Q000097:blood; D020552:Comet Assay; D004249:DNA Damage; D005204:Farnesol / Q000494:pharmacology*; D022781:Hepatocytes / Q000378:metabolism; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013729:Terpenes / Q000494:pharmacology*
D000080462:Acyclic Monoterpenes; D016588:Anticarcinogenic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013729:Terpenes; D005204:Farnesol; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; C007836:geraniol