title: Naringenin ameliorates inflammation and cell proliferation in benzo(a)pyrene induced pulmonary carcinogenesis by modulating CYP1A1, NFκB and PCNA expression.
abstract: Lung cancer is the major cause of cancer-related mortality and is a growing economic burden worldwide. Chemoprevention has emerged as a very effective preventive measure against carcinogenesis and several bioactive compounds in diet have shown their cancer curative potential on lung cancer. Naringenin (NRG), a predominant flavanone found in citrus fruits has been reported to possess anti-oxidative, anti-inflammatory and anti-proliferative activity in a wide variety of cancer. The aim of the present study is to divulge the chemopreventive nature of NRG against benzo(a)pyrene (B[a]P) induced lung carcinogenesis in Swiss albino mice. Administration of B[a]P (50mg/kg, p.o.) to mice resulted in increased lipid peroxidation (LPO), proinflammatory cytokines (TNF-α, IL-6 and IL-1β) with subsequent decrease in activities of tissue enzymic antioxidants (SOD, CAT, GPx, GR, GST) and non-enzymic antioxidants (GSH and Vit-C). Treatment with NRG (50mg/kg body weight) significantly counteracted all these alterations thereby showing potent anti-cancer effect in lung cancer. Moreover, assessment of protein expression by immunoblotting and mRNA expression by RT-PCR revealed that NRG treatment effectively negates B[a]P-induced upregulated expression of CYP1A1, PCNA and NF-κB. Further, the antiproliferative effect of NRG was confirmed by histopathological analysis and PCNA immunostaining in B[a]P induced mice which showed increased PCNA expression that was restored upon NRG administration. Overall, these findings substantiate the chemopreventive potential of NRG against chemically induced lung cancer in mice.
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam 781032, India. Electronic address: laxmi.naren21@gmail.com.
authors.forename: Lakshmi Narendra
authors.initials: LN
authors.lastname: Bodduluru
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam 781032, India.
authors.forename: Eshvendar Reddy
authors.initials: ER
authors.lastname: Kasala
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam 781032, India.
authors.forename: Rajaram Mohanrao
authors.initials: RM
authors.lastname: Madhana
authors.affiliation: Department of Pharmacology and Toxicology, College of Veterinary Science, Assam Agricultural University, Guwahati, Assam 781032, India.
authors.forename: Chandana C
authors.initials: CC
authors.lastname: Barua
authors.affiliation: State Biotech Hub, College of Veterinary Science, Assam Agricultural University, Khanapara, Guwahati, Assam 781022, India.
authors.forename: Md Iftikar
authors.initials: MI
authors.lastname: Hussain
authors.affiliation: Department of Pharmacology and Toxicology, College of Veterinary Science, Assam Agricultural University, Guwahati, Assam 781032, India.
authors.forename: Prakash
authors.initials: P
authors.lastname: Haloi
authors.affiliation: State Biotech Hub, College of Veterinary Science, Assam Agricultural University, Khanapara, Guwahati, Assam 781022, India.
authors.forename: Probodh
authors.initials: P
authors.lastname: Borah
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D001580:Benzopyrenes / Q000008:administration & dosage; D063646:Carcinogenesis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002957:Citrus / Q000276:immunology; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D044950:Flavanones / Q000008:administration & dosage*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000139:chemically induced; D010084:Oxidation-Reduction / Q000187:drug effects; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001580:Benzopyrenes; D016207:Cytokines; D044950:Flavanones; D016328:NF-kappa B; D018809:Proliferating Cell Nuclear Antigen; D019363:Cytochrome P-450 CYP1A1; C005273:naringenin
keywords: Benzo[a]pyrene; Chemoprevention; Lung cancer; NF-κB; Naringenin