The effects of topical L-selenomethionine on protection against UVB-induced skin cancer when given before, during, and after UVB exposure

Authors: BURKE, KAREN - Mount Sinai School Of Medicine; ZHOU, XUEYAN - Mount Sinai School Of Medicine; WANG, YONGYIN - Mount Sinai School Of Medicine; COMMISSO, JOEL - University Of California; KEEN, CARL - University Of California; NAKAMURA, ROBERT - Scripps Institute; Combs, Gerald; WEI, HUACHEN - Mount Sinai School Of Medicine

Submitted to: Journal of Clinical Investigation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/19/2014
Publication Date: 10/13/2014
Publication URL: http://handle.nal.usda.gov/10113/60281
Citation: Burke, K.E., Zhou, X., Wang, Y., Commisso, J., Keen, C.L., Nakamura, R.M., Combs, G.F., Wei, H. 2014. The effects of topical L-selenomethionine on protection against UVB-induced skin cancer when given before, during, and after UVB exposure. Journal of Clinical Investigation. 13(10):1214-1223.

Interpretive Summary: Many studies have shown that the essential nutrient selenium (Se) can prevent tumorigenesis in animal models. Most such studies have used forms of Se provided in food; only few have addressed the question of whether Se compounds applied to the skin may also protect against cancer, particularly those of the skin. Our team previous found that Se can be absorbed by the skin when applied topically, and that topical application of L-selenomethionine (SeMet) can prevent skin cancer induced by ultraviolet-B (UVB) light. We conducted this experiment to learn whether the timing of SeMet application affect its capacity to inhibit UVB-tumorigenesis, as that information will inform prospects for practical use of Se for prevention of skin cancer. Specifically, we wanted to learn whether topical SeMet is most protective if applied (a) before, during and after UVB exposure, (b) until tumors are detected, or (c) after tumors are detected. We applied SeMet in a skin lotion (0.05%) with an unsupplemented lotion as a control, both applied to the backs of hairless, non-pigmented mice given measured exposures to UV radiation, which was discontinued when the first tumor was detected. Results showed that optimal inhibition of skin cancer was achieved by applying topical SeMet continuously, and that application after the onset of tumors also conferred protection. These results suggest that SeMet supplementation even late in the process of tumorigenesis can help protect from UV-induced photodamage and skin cancer.

Technical Abstract: Previous studies in mice have shown that topical L-selenomethionine (SeMet) can prevent UVB-induced skin cancer when applied continuously before, during, and after the radiation exposure. With topical application of SeMet, selenium levels were shown to increase in the skin and liver, as well as in tumor tissue. Thus, possibly, the timing of SeMet application could affect the degree of inhibition of UVB-tumorigenesis (or maybe even enhance tumorigenesis at some stage). The goal of this research was to determine whether topical SeMet best inhibits UV-induced skin cancer if (a) begun before and continued during and after UVB exposure, (b) if begun before UVB-exposure and discontinued when tumors are first clinically detected, or (c) if begun only after tumors are first detected and continued thereafter. Groups of ten Skh:1 hairless, non-pigmented mice were treated topically with vehicle lotion, or with SeMet (0.05%) in that vehicle lotion applied either (a) before, during, and after UV exposure, (b) before UV radiation and continued only until the first tumor was detected , or (c) only after the first tumor was detected. In all cases, UV irradiation was discontinued at the time of detection of the first tumor. Optimal inhibition of skin cancer was achieved by application of topical SeMet before, during, and after exposure; significant protection was also attained with application only after the onset of tumors. Notably, statistically significant protection was not seen with SeMet application only prior to tumor detection. These results suggest that even beginning SeMet supplementation late in the process of tumorigenesis can help protect from UV-induced photodamage and skin cancer.