The Effects of Topical L-Selenomethionine on Protection Against UVB-Induced Skin Cancer When Given Before, During, and After UVB Exposure

October 2014 | Volume 13 | Issue 10 | Original Article | 1214 | Copyright © 2014

Karen E. Burke,a Xueyan Zhou,a Yongyin Wang,f Joel Commisso,b Carl L. Keenb
Robert M. Nakamura,a Gerald F. Combs Jr.,d and Huachen Weia,e

aDepartment of Dermatology, The Mount Sinai Medical Center, New York, NY
bDepartment of Nutrition, University of California at Davis, CA
cDepartment of Pathology, Scripps Clinic and Research Foundation, La Jolla, CA (Deceased)
dCenter Director, Grand Forks Human Nutrition Research Center, USDA-ARS, Grand Forks, ND
eDepartment of Dermatology, No.1 Hospital, China Medical University, Shenyang, China
fMedtronic, Inc., Diabetes Group, Northridge, CA

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.

J Drugs Dermatol. 2014;13(10):1214-1223.

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INTRODUCTION

Selenium (Se) is an essential trace element for human and animal health. Se is a specific component of twenty-five selenoproteins and Se-dependent enzymes that play roles in antioxidant defense, reduction of inflammation, thyroid hormone metabolism, lipid metabolism, thermogenesis, DNA synthesis, gene transcription, fertility, fetal brain development and reproduction,1,2 and both humoral and cellular immunity.3,4 Selenium metabolites have been shown to impair angiogenesis by tumors5,6 and to promote cell cycle arrest and apoptosis of tumor cells,7 as well as inhibit local invasion and migration.6,8 That Se can inhibit malignant spreading was demonstrated by Yan and colleagues for several oral forms of the element: methylseleninic acid,6 selenite,8 high-Se soy protein.9 Their work showed that this effect involves reducing adhesion of cancer cells to extracellular matrix,10 inhibiting the urokinase plasminogen activator (uPA) system6 and reducing angiogenesis.6 Selenium metabolites further enhance metabolism of foreign compounds including carcinogen-detoxifying enzymes.11 Epidemiological studies12,13,14 have shown inverse correlations between soil Se levels and cancer mortality rates. Several early, retrospective case studies detected significant inverse correlations of the incidence of internal neoplasms with blood Se concentrations.14,15,16,17 However, such data are difficult to interpret because of the possibilities (a) that the cancer can affect the general nutritional status and, therefore, the Se status of patients, and (b) that the neoplastic tissue may sequester Se.

Because skin cancers rarely affect general nutritional status, epidemiologic data on correlations with skin cancer are particularly interesting. For example, patients with malignant melanoma were found to have significantly lower levels of serum Se; indeed, patients with more advanced disease (stage III disseminated melanoma) had the lowest levels.18 In a transgenic mouse model, topical treatment with SeMet resulted in a significant delay in the time required for melanoma development (though established tumors grew more rapidly).19 A recent

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