Effects of perillyl alcohol on melanoma in the TPras mouse model.

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 Ras. POH (10 mM) was applied to the shaved dorsal skin of TPras mice starting 1 week before five treatments of dimethylbenz[a]anthracene (50 microg) 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, mitogen-activated 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.

• Authors: Maria Lluria-Prevatt, Jeanne Morreale, Jacie Gregus, David S Alberts, Fiona Kaper, Amato Giaccia, Marianne Broome Powell
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 11 Issue 6 Pg. 573-9 (Jun 2002) ISSN: 1055-9965 [Print] United States
• PMID: 12050099 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Monoterpenes
• Terpenes
• perillyl alcohol
• ras Proteins

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Disease Models, Animal
• Female
• Male
• Melanoma (prevention & control, veterinary)
• Mice
• Mice, Transgenic
• Monoterpenes
• Signal Transduction
• Skin Neoplasms (prevention & control, veterinary)
• Terpenes (pharmacology)
• Tumor Cells, Cultured (drug effects)
• ras Proteins (biosynthesis, genetics)