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Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)
04:12

Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)

Published on: December 19, 2019

Geraniol inhibits murine skin tumorigenesis by modulating COX-2 expression, Ras-ERK1/2 signaling pathway and

Sandeep Chand Chaudhary1, Mohammad Saeed Siddiqui, Mohammad Athar

  • 1Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi-110062, India.

Journal of Applied Toxicology : JAT
|July 5, 2012
PubMed

Insights

Geraniol (GOH) shows significant potential as a cancer chemopreventive agent. This study found GOH effectively inhibited skin tumor development in mice by reducing inflammation and promoting apoptosis.

Area of Science:

  • Oncology
  • Chemoprevention
  • Molecular Biology

Background:

  • Geraniol (GOH), a natural monoterpene, exhibits antiproliferative and apoptosis-inducing properties.
  • GOH is recognized as a promising agent for cancer chemoprevention.

Purpose of the Study:

  • To investigate the chemopreventive efficacy of Geraniol (GOH) against 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol 13-acetate (TPA)-induced skin tumorigenesis in Swiss albino mice.
  • To elucidate the molecular mechanisms underlying GOH's chemopreventive effects.

Main Methods:

  • Mice were topically treated with GOH (50 and 100 mg/kg body weight) prior to TPA administration.
  • Key markers of skin tumorigenesis, including edema, hyperplasia, COX-2 induction, ornithine decarboxylase activity, and thymidine incorporation, were assessed.
  • The study analyzed the Ras/Raf/ERK1/2 signaling pathway and the expression of apoptosis-related proteins (Bcl-2, Bax).

Main Results:

  • GOH treatment significantly inhibited TPA-induced skin edema, hyperplasia, COX-2, and oxidative stress.
  • GOH reduced ornithine decarboxylase activity by 53% and thymidine incorporation by 41%.
  • GOH significantly suppressed tumor incidence and number, extending latency, and attenuated the Ras/Raf/ERK1/2 pathway, while modulating Bcl-2 and Bax expression.

Conclusions:

  • Geraniol (GOH) effectively inhibits DMBA/TPA-mediated skin tumorigenesis in mice.
  • GOH's chemopreventive action is attributed to the attenuation of the Ras proliferation pathway and induction of apoptosis.
  • GOH exerts its effects by inhibiting oxidative stress and inflammation, highlighting its therapeutic potential.

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