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

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 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.

• Authors: Sandeep Chand Chaudhary, Mohammad Saeed Siddiqui, Mohammad Athar, Mohammad Sarwar Alam
• Journal: Journal of applied toxicology : JAT (J Appl Toxicol) Vol. 33 Issue 8 Pg. 828-37 (Aug 2013) ISSN: 1099-1263 [Electronic] England
• PMID: 22760862 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 John Wiley & Sons, Ltd.

Chemical References

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

Topics

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