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Published on: August 10, 2021
Geraniol attenuates 4NQO-induced tongue carcinogenesis through downregulating the activation of NF-κB in rats
Arumugam Madankumar1,2, Sasivarnam Tamilarasi3, Thandavamoorthy Premkumar3
1Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600025, India. madankumarbio@gmail.com.
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.
Insights
Geraniol, a natural compound, shows promise in preventing oral cancer by reducing inflammation. It inhibits the nuclear factor-kappa B (NF-κB) pathway, a key driver of inflammation in cancer development.
Area of Science:
- * Pharmacology
- * Molecular Biology
- * Cancer Research
Background:
- * Geraniol, an acyclic monoterpene from lemongrass, exhibits antitumor and antioxidant properties.
- * Oral carcinogenesis is often associated with inflammation and specific signaling pathways.
- * Nuclear Factor-kappa B (NF-κB) signaling plays a crucial role in inflammatory responses and cancer progression.
Purpose of the Study:
- * To evaluate the chemoprotective effect of geraniol against 4-nitroquinoline-1-oxide (4NQO)-induced oral cancer in rats.
- * To elucidate the anti-inflammatory mechanisms of geraniol, focusing on the NF-κB signaling pathway.
- * To investigate geraniol's impact on inflammatory mediators and mast cell activity during oral carcinogenesis.
Main Methods:
- * Oral carcinogenesis was induced in male Wistar rats using 4-nitroquinoline-1-oxide (4NQO) at 50 ppm in drinking water for 20 weeks.
- * Geraniol (200 mg/kg body weight) was administered as a co-treatment.
- * Key inflammatory markers including p65 NF-κB, TNF-α, IL-1β, COX-2, and iNOS were quantified.
- * Mast cell density was assessed using toluidine blue and alcian blue-safranin staining.
Main Results:
- * 4NQO administration significantly upregulated NF-κB, TNF-α, IL-1β, COX-2, and iNOS, alongside increased mast cell accumulation.
- * Geraniol co-treatment markedly reduced nuclear p65 NF-κB levels, suggesting inhibition of NF-κB activation.
- * Geraniol decreased the density of immature and mature mast cells and downregulated the expression of inflammatory mediators.
Conclusions:
- * Geraniol demonstrates significant chemoprotective potential against 4NQO-induced oral carcinogenesis.
- * Geraniol exerts anti-inflammatory effects by inhibiting NF-κB activation and subsequent downstream signaling.
- * Geraniol's modulation of inflammatory mediators and mast cells contributes to its protective role in oral cancer prevention.
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