title: Geraniol attenuates 4NQO-induced tongue carcinogenesis through downregulating the activation of NF-κB in rats.
abstract: Geraniol, an acyclic monoterpene found in lemon grass and aromatic herb oil, has been shown to exert antitumor and antioxidant activities against various cancer types. The objective of this study was to investigate the potential chemoprotective role of geraniol against 4-nitroquinoline-1-oxide (4NQO)-induced oral carcinogenesis in male Wistar rats and furthermore to study anti-inflammatory mechanisms of action through possible NF-κB signaling. 4NQO was administered to rats at the dose of 50 ppm through drinking water to induce tongue cancer in 20 weeks. 4NQO provoked inflammation by upregulating the expressions of the p65 subunit nuclear factor kappa-β (NF-κB) in the nucleus, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). Additionally, staining for immature and mature mast cells in cancer niche by toluidine blue staining and alcian blue-safranin staining showed more accumulation. Co-treatment of geraniol 200 mg/kg b.w. showed a significant decrease in the level of p65 NF-κB in the nucleus, and this might be due to the inhibition of NF-κB activation/translocation into nucleus, which was further confirmed by decreased immature and mature mast cell density and the expression of inflammatory downstream mediators such as TNF-α, IL-1β, COX-2, and iNOS. Collectively, our results suggested that geraniol as a potential anti-inflammatory agent having the capability to obstruct 4NQO initiated NF-κB activation and modulated the expression of inflammatory mediators.
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600025, India. madankumarbio@gmail.com.|Cancer Biology Lab, Molecular and Nanomedicine Research Unit, Sathyabama University, Chennai, 600119, India. madankumarbio@gmail.com.
authors.forename: Arumugam
authors.initials: A
authors.lastname: Madankumar
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600025, India.
authors.forename: Sasivarnam
authors.initials: S
authors.lastname: Tamilarasi
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600025, India.
authors.forename: Thandavamoorthy
authors.initials: T
authors.lastname: Premkumar
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600025, India.
authors.forename: Mani
authors.initials: M
authors.lastname: Gopikrishnan
authors.affiliation: Cancer Biology Lab, Molecular and Nanomedicine Research Unit, Sathyabama University, Chennai, 600119, India.
authors.forename: Natesh
authors.initials: N
authors.lastname: Nagabhishek
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600025, India.
authors.forename: Thiruvengadam
authors.initials: T
authors.lastname: Devaki
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity; D000080462:Acyclic Monoterpenes; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001772:Blood Cell Count; D015153:Blotting, Western; D002273:Carcinogens / Q000633:toxicity*; D015536:Down-Regulation / Q000187:drug effects*; D007249:Inflammation / Q000150:complications / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D015363:Quinolones / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013729:Terpenes / Q000494:pharmacology*; D014062:Tongue Neoplasms / Q000139:chemically induced / Q000150:complications / Q000378:metabolism / Q000517:prevention & control*
chemical_list: C120195:4-nitroquinolone-1-oxide; D000080462:Acyclic Monoterpenes; D016588:Anticarcinogenic Agents; D002273:Carcinogens; D018836:Inflammation Mediators; D016328:NF-kappa B; D015363:Quinolones; D013729:Terpenes; D015112:4-Nitroquinoline-1-oxide; C007836:geraniol
keywords: 4-Nitroquinoline-1-oxide; Geraniol; Inflammation; Mast cells; NF-κB; Tumor necrosis factor-α