title: Garlic Oil Suppressed Nitrosodiethylamine-Induced Hepatocarcinoma in Rats by Inhibiting PI3K-AKT-NF-κB Pathway.
abstract: To explore the underlying mechanisms for the protective effects of garlic oil (GO) against nitrosodiethylamine (NDEA)-induced hepatocarcinoma, 60 male Wistar rats were randomized into 4 groups (n=15): control group, NDEA group, and two GO plus NDEA groups. The rats in GO plus NDEA groups were pretreated with GO (20 or 40 mg/kg) for 7 days. Then, all rats except those in control group were gavaged with NDEA for 20 weeks, and the rats in GO plus NDEA groups were continuously administered with GO. The results showed that GO co-treatment significantly suppressed the NDEA-induced increases of alpha fetal protein (AFP) level in serum, nuclear atypia in H&E staining, sirius red-positive areas and proliferating cell nuclear antigen (PCNA) expression. The molecular mechanisms exploration revealed that the protein levels of phosphatidylinositol 3 kinase (PI3K)-p85, PI3K-p110, total AKT, p-AKT (Ser473) and p-AKT (Thr308) in the liver of NDEA group rats were higher than those in control group rats. In addition, NDEA treatment induced IκB degradation and NF-κB p65 phosphorylation, and up-regulated the protein levels of downstream pro-inflammatory mediators. GO co-treatment significantly reversed all the above adverse effects induced by NDEA. These results suggested that the protective effects of GO against NDEA-induced hepatocarcinoma might be associated with the suppression of PI3K- AKT-NF-κB pathway.
authors.affiliation: Institute of Toxicology, School of Public Health, Shandong University, 44 Wenhua West Road, Jinan 250012, Shandong, P.R. China.
authors.forename: Cui-Li
authors.initials: CL
authors.lastname: Zhang
authors.affiliation: Institute of Toxicology, School of Public Health, Shandong University, 44 Wenhua West Road, Jinan 250012, Shandong, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zeng
authors.affiliation: Institute of Toxicology, School of Public Health, Shandong University, 44 Wenhua West Road, Jinan 250012, Shandong, P.R. China.
authors.forename: Xiu-Lan
authors.initials: XL
authors.lastname: Zhao
authors.affiliation: Institute of Toxicology, School of Public Health, Shandong University, 44 Wenhua West Road, Jinan 250012, Shandong, P.R. China.
authors.forename: Ke-Qin
authors.initials: KQ
authors.lastname: Xie
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D002277:Carcinoma / Q000139:chemically induced*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004052:Diethylnitrosamine / Q000633:toxicity*; D020672:I-kappa B Proteins / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced*; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013440:Sulfides / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000378:metabolism*
chemical_list: C483800:Afp protein, rat; D000498:Allyl Compounds; D020672:I-kappa B Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D029543:Nucleocytoplasmic Transport Proteins; D020011:Protective Agents; D013440:Sulfides; D042461:Vascular Endothelial Growth Factor A; D000509:alpha-Fetoproteins; C063447:p65 oncofetal mRNA transport protein, rat; C467498:vascular endothelial growth factor A, rat; D004052:Diethylnitrosamine; C038491:allyl sulfide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT; Garlic oil; Hepatocarcinoma; NF-κB; Nitrosodiethylamine; Phosphatidylinositol 3 kinase (PI3K)