title: Attenuation of NDEA-induced hepatocarcinogenesis by naringenin in rats.
abstract: Chemoprevention is one of the most promising and realistic approaches in the prevention of cancer. Several bioactive compounds present in fruits and vegetables have revealed their cancer curative potential on hepatocellular carcinoma. Naringenin is one such naturally occurring flavonoid widely found in citrus fruits. In this study, we examined the molecular mechanisms by which naringenin inhibited NDEA-induced hepatocellular carcinoma in rats by analysing the expression patterns of proliferating cell nuclear antigen, Bcl-2, NF-κB, VEGF and MMP-2/9. Enhanced cell proliferation and apoptotic evasion in NDEA-induced hepatocarcinogenesis was associated with imbalance in pro-apoptotic and anti-apoptotic proteins together with upregulation of proliferating cell nuclear antigen (PCNA) and downregulation of caspase-3. Administration of pretreatment and posttreatment of naringenin decreased the expression of PCNA and Bcl-2 and increased the expression of Bax and caspase-3, indicating antiproliferative and apoptotic effects, respectively. Administration of NDEA increased the tumour expression of NF-κB, COX-2, VEGF, MMP-2 and MMP-9 that was correlated with more aggressive lesions and tumour growth. Downregulation of NF-κB, VEGF and MMPs by naringenin seen in the present study were correlated with the inhibition of liver tumour induced by NDEA. Our results suggest that naringenin could act as a legitimate agent by inhibiting cancer processes.
authors.affiliation: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Tamil Nadu, India. psub@rediffmail.com
authors.forename: Perumal
authors.initials: P
authors.lastname: Subramanian
authors.forename: Duraikannu
authors.initials: D
authors.lastname: Arul
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D063646:Carcinogenesis / Q000187:drug effects* / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D044950:Flavanones / Q000008:administration & dosage*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008113:Liver Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D009602:Nitrosamines / Q000633:toxicity; D051381:Rats; D015854:Up-Regulation
chemical_list: D044950:Flavanones; D009602:Nitrosamines; C044516:N-nitrosobis(2,2,2-trifluoroethyl)amine; C005273:naringenin