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

Academic Article

Abstract

  • 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 100mgkg-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, 30min prior to TPA (2μg per 200μl 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 [3H] 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 4weeks in DMBA/TPA treatment group to 10weeks 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. © 2012 John Wiley & Sons, Ltd.
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    Digital Object Identifier (doi)

    Author List

  • Chaudhary SC; Siddiqui MS; Athar M; Alam MS
  • Start Page

  • 828
  • End Page

  • 837
  • Volume

  • 33
  • Issue

  • 8