title: 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: Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi-110062, India.
authors: Sandeep Chand
authors: SC
authors: Chaudhary
authors: Mohammad Saeed
authors: MS
authors: Siddiqui
authors: Mohammad
authors: M
authors: Athar
authors: Mohammad Sarwar
authors: MS
authors: Alam
mesh_terms: D000080462:Acyclic Monoterpenes; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D063646:Carcinogenesis / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D004487:Edema / Q000517:prevention & control; D005260:Female; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000473:pathology; D013729:Terpenes / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000080462:Acyclic Monoterpenes; D016588:Anticarcinogenic Agents; C494827:Bax protein, mouse; D013729:Terpenes; D051028:bcl-2-Associated X Protein; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D018631:ras Proteins; C007836:geraniol; D013755:Tetradecanoylphorbol Acetate