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.

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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