Inhibitory effects of perillyl alcohol on UVB-induced murine skin cancer and AP-1 transactivation.
The monoterpene perillyl alcohol (POH) has proven efficacious against the formation and progression of a variety of cancers. In this study, we tested the ability of POH to inhibit photocarcinogenesis in a nonmelanoma model of mouse skin carcinogenesis and its ability to inhibit UVB-induced activator protein 1 (AP-1) transactivation in mouse skin and human keratinocytes. POH (10 mM) was applied topically to the ears and shaved dorsal surface of groups of 35 BALB/c mice throughout the experiment, during and after UVB treatment. Topical POH significantly inhibited tumor incidence and multiplicity, average tumor size, and the average tumor burden/mouse without any apparent toxicity. POH inhibited UVB-induced AP-1 transactivation in both cultured human keratinocytes and transgenic mice that stably express a luciferase reporter driven by AP-1 elements. The results suggest that POH might be used for chemoprevention of human skin cancer, and that inhibition of AP-1 activity is functionally related to inhibition of skin carcinogenesis.
Barthelman
M
M
Department of Radiation Oncology, The University of Arizona Health Sciences Center, Tucson 85724, USA.
Chen
W
W
Gensler
H L
HL
Huang
C
C
Dong
Z
Z
Bowden
G T
GT
D000287:Administration, Topical; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D039821:Monoterpenes; D009381:Neoplasms, Radiation-Induced / Q000517:prevention & control*; D012878:Skin Neoplasms / Q000517:prevention & control*; D013729:Terpenes / Q000008:administration & dosage / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015533:Transcriptional Activation; D014466:Ultraviolet Rays
D039821:Monoterpenes; D013729:Terpenes; D018808:Transcription Factor AP-1; C032208:perillyl alcohol