Naringenin ameliorates inflammation and cell proliferation in benzo(a)pyrene induced pulmonary carcinogenesis by modulating CYP1A1, NFκB and PCNA expression

• Naringenin exerts chemopreventive effect in B[a]P induced pulmonary carcinogenesis.
• Naringenin treatment restored the lipid peroxidation and antioxidants to near normalcy.
• Naringenin modulates the B[a]P induced inflammatory cytokines in the lung.
• Naringenin downregulated the B[a]P-induced CYP1A1, NF-κB and PCNA expression.
• Naringenin protects pulmonary architecture in mice with experimental lung cancer.

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 (50 mg/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 (50 mg/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.