Geraniol inhibits murine skin tumorigenesis by modulating COX‐2 expression, Ras‐ERK1/2 signaling pathway and apoptosis. Issue 8 (4th July 2012)

• Record Type: Journal Article
• Authors: Chaudhary, Sandeep Chand; Siddiqui, Mohammad Saeed; Athar, Mohammad; Alam, Mohammad Sarwar
• Is Part Of: Journal of applied toxicology. Volume 33:Issue 8(2013)
• Page Start: 828
• Page End: 837
• Publication Date: 2012-07-04
• Subjects: Toxicology -- Periodicals; Industrial toxicology -- Periodicals; Environmentally induced diseases -- Periodicals; Toxicology -- Periodicals; 615.9005
• DOI: 10.1002/jat.2739
• Languages: English
• ISSNs: 0260-437X

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p>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<sup>−1</sup> body weight) against 7, 12‐dimethylbenz[a]anthracene (DMBA)/12‐<italic>O</italic>‐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 [<sup>3</sup>H] thymidine incorporation by 53% (<italic>P</italic> < 0.001) and 41% (<italic>P</italic> < 0.001), respectively. We found that GOH treatment significantly inhibited the tumor incidence and number of tumors (<italic>P</italic> < 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. Copyright © 2012 John Wiley & Sons, Ltd.</p> </abstract>