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

J Appl Toxicol. 2013 Aug;33(8):828-37. doi: 10.1002/jat.2739. Epub 2012 Jul 4.


Geraniol (GOH), a naturally occurring monoterpene, has been shown to have antiproliferative, cell cycle arrest and apoptosis-inducing effects, and represents a promising cancer chemopreventive agent. In the present study, we investigated the chemopreventive potential of GOH (50 and 100 mg kg(-1) body weight) against 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol 13-acetate (TPA)-mediated skin tumorigenesis in Swiss albino mice. The topical treatment of GOH, 30 min prior to TPA (2 µg per 200 µl of acetone) treatment significantly inhibited TPA-induced skin edema, hyperplasia, COX-2 induction and oxidative stress response. The GOH treatment also resulted in reduction of TPA-induced ornithine decarboxylase activity and [(3) H] thymidine incorporation by 53% (P < 0.001) and 41% (P < 0.001), respectively. We found that GOH treatment significantly inhibited the tumor incidence and number of tumors (P < 0.001) and extended the latency period from 4 weeks in DMBA/TPA treatment group to 10 weeks in GOH-pretreated mice. Furthermore, we observed that GOH treatment significantly suppressed the Ras/Raf/ERK1/2 signaling pathway in skin tumor. Consistently, GOH-treated skin tumors showed reduced expression of Bcl-2 and increased expression of Bax in these lesions. Thus, it was concluded that GOH inhibits DMBA/TPA-mediated skin tumorigenesis by attenuating the Ras proliferation pathway and inducing pro-apoptotic state via inhibition of oxidative stress response and inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyclic Monoterpenes
  • Animals
  • Anticarcinogenic Agents / pharmacology
  • Apoptosis / drug effects*
  • Carcinogenesis / drug effects*
  • Cyclooxygenase 2 / genetics*
  • Cyclooxygenase 2 / metabolism
  • Edema / prevention & control
  • Female
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • MAP Kinase Signaling System / drug effects
  • Mice
  • Oxidative Stress / drug effects
  • Skin / drug effects
  • Skin / pathology
  • Terpenes / pharmacology*
  • Tetradecanoylphorbol Acetate / metabolism
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism
  • ras Proteins / genetics
  • ras Proteins / metabolism


  • Acyclic Monoterpenes
  • Anticarcinogenic Agents
  • Bax protein, mouse
  • Terpenes
  • bcl-2-Associated X Protein
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • ras Proteins
  • geraniol
  • Tetradecanoylphorbol Acetate