期刊
CHEMICO-BIOLOGICAL INTERACTIONS
卷 179, 期 2-3, 页码 145-153出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2008.12.016
关键词
Perillyl alcohol; Oxidative stress; Ras pathway; Apoptosis; Skin tumorigenesis
资金
- Council of Medical Research (ICMR), New Delhi
In the present study, the chemopreventive effect of topical application of perillyl alcohol (POH) on 9,10-dimethylbenz(a)anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumorigenesis and its possible mechanisms of action in Swiss albino mice were investigated. We evaluated the effect of pretreatment of POH (6 and 12 mg/kg body weight) on TPA (2 mu g/200 mu l of acetone)-induced skin edema, hyperplasia, peroxidase damage and modulation in activities of catalase, glutathione reductase, glutathione peroxidase, glutathione-S-transferase and reduced glutathione contents. Application of POH 30 min prior to TPA treatment, showed a protective effect in almost all the investigated parameters. Additionally, pretreatment with POH showed a significant: inhibition of ornithine decarboxylase (ODC) activity and [H-3] thymidine incorporation into epidermal DNA. In promotion phase, a significant reduction was found in tumor incidence and tumor burden in mice pretreated with POH (12 mg/kg body weight) with extension of the latency period from 4 to 8 weeks as compared to those treated with TPA alone. POH significantly suppressed the Ras/Raf/ERK pathway and induced apoptosis in Swiss albino mice skin. Our findings suggested that the chemopreventive efficacy of POH is probably due to the inhibition of oxidative stress responses, inhibition of the Ras cell proliferation pathway and induction of apoptosis in murine skin tumor promotion phase. (c) 2009 Elsevier Ireland Ltd. All rights reserved.
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