Effects of perillyl alcohol on melanoma in the TPras mouse model

Maria Lluria-Prevatt, Jeanne Morreale, Jacie Gregus, David S. Alberts, Fiona Kaper, Amato Giaccia, Marianne Broome Powell

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

This study evaluates the chemopreventive effects of topically applied perillyl alcohol on the development of melanoma in TPras transgenic mice. Our strategy was to target critical pathways in the development of melanoma, in particular, the ras pathway. Ras has been shown in our experimental mouse model, as well as others, to be important in the development and maintenance of melanomas. Perillyl alcohol (POH), a naturally occurring monoterpene, inhibits the isoprenylation of small G protein, including Res. POH (10 mM) was applied to the shaved dorsal skin of TPras mice starting l week before five treatments of dimethylbenz[a]anthracene (50 μg) and was continued for 38 weeks. We observed a delay in the appearance of tumors and a 25-35% reduction in melanoma incidence. POH treatment of melanoma cells in vitro reduced the levels of detectable Ras protein and inhibits the activation of downstream targets, mitogenactivated protein kinases and Akt. POH only minimally induced apoptosis in this system. Pretreatment but not post-treatment of the melanoma cells with POH, however, markedly reduced levels of UV-induced reactive oxygen species. These studies suggest that POH inhibition of the Ras signaling pathway may be an effective target for chemoprevention of melanoma.

Original languageEnglish (US)
Pages (from-to)573-579
Number of pages7
JournalCancer Epidemiology Biomarkers and Prevention
Volume11
Issue number6
StatePublished - 2002

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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    Lluria-Prevatt, M., Morreale, J., Gregus, J., Alberts, D. S., Kaper, F., Giaccia, A., & Powell, M. B. (2002). Effects of perillyl alcohol on melanoma in the TPras mouse model. Cancer Epidemiology Biomarkers and Prevention, 11(6), 573-579.