title: Curcumin inhibits B[a]PDE-induced procarcinogenic signals in lung cancer cells, and curbs B[a]P-induced mutagenesis and lung carcinogenesis.
abstract: Benzo[a]pyrene is a procarcinogen present in environment and cigarette smoke, which could be bio-transformed in vivo to B[a]PDE, a potent carcinogen known to form DNA adducts and induce mutations. We observed that curcumin, a known chemopreventive, could significantly inhibit the survival of lung cancer cells exposed to B[a]PDE. It also downregulates B[a]PDE-induced nuclear translocation of NF-κB as assessed by Electrophoretic Mobility Shift Assay (EMSA) and NF-κB-dependent reporter gene assay. Ames assay demonstrated its ability to revert the mutagenic property of benzo[a]pyrene. These observations prompted us to evaluate the efficacy of curcumin in preventing B[a]P-induced lung carcinogenesis in vivo and to explore the molecular mechanism associated with it. The average number of tumor nodules present in the lungs of the Swiss albino mice, which received benzo[a]pyrene, was significantly high compared to that received curcumin as 2% diet along with B[a]P. Curcumin treatment significantly reverted histopathological deviations in the lung tissues due to benzo[a]pyrene ingestion. Moreover, curcumin diet reduced benzo[a]pyrene-induced activation of NF-κB and MAPK signaling and Cox-2 transcription in lung tissues of mice. Taken together, this study illustrates multifaceted efficacy of curcumin in preventing lung cancer.
authors.affiliation: Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, 695014, India.
authors.forename: Vineshkumar T
authors.initials: VT
authors.lastname: Puliyappadamba
authors.affiliation: Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, 695014, India.
authors.forename: Arun Kumar T
authors.initials: AK
authors.lastname: Thulasidasan
authors.affiliation: Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, 695014, India.
authors.forename: Vinod
authors.initials: V
authors.lastname: Vijayakurup
authors.affiliation: Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, 695014, India.
authors.forename: Jayesh
authors.initials: J
authors.lastname: Antony
authors.affiliation: Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, 695014, India.
authors.forename: Smitha V
authors.initials: SV
authors.lastname: Bava
authors.affiliation: Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, 695014, India.
authors.forename: Shabna
authors.initials: S
authors.lastname: Anwar
authors.affiliation: Department of Pathology, Government Medical College, Thiruvananthapuram, Kerala, 695011, India.
authors.forename: Sankar
authors.initials: S
authors.lastname: Sundaram
authors.affiliation: Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, 695014, India.
authors.forename: Ruby John
authors.initials: RJ
authors.lastname: Anto
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000633:toxicity; D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity; D001711:Biotransformation; D063646:Carcinogenesis / Q000187:drug effects / Q000235:genetics*; D003474:Curcumin / Q000008:administration & dosage*; D018736:DNA Adducts / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced / Q000178:diet therapy* / Q000235:genetics* / Q000473:pathology; D051379:Mice; D016296:Mutagenesis / Q000187:drug effects / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics
chemical_list: D018736:DNA Adducts; D016328:NF-kappa B; D001564:Benzo(a)pyrene; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D003474:Curcumin
keywords: B[a]PDE; Benzo[a]pyrene; NF-κB; curcumin; lung cancer