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Selenium for the Prevention of Cutaneous Melanoma
Department of Medicinal Chemistry, Huntsman Cancer Institute, 2000 Circle of Hope, Salt Lake City, UT 84112, USA
Department of Dermatology, Huntsman Cancer Institute, 2000 Circle of Hope, Salt Lake City, UT 84112, USA
University of Utah School of Medicine, 50 North Campus Dr., Salt Lake City, UT 84112, USA
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112, USA
Biostatistics Unit, Huntsman Cancer Institute, 2000 Circle of Hope, Salt Lake City, UT 84112, USA
Applied Speciation, 18804 Northcreek Parkway, Bothell, WA 98011, USA
Department of Dermatology, University of Utah School of Medicine, 50 North Campus Dr., Salt Lake City, UT 84112, USA
Department of Oncological Sciences, Huntsman Cancer Institute, 2000 Circle of Hope, Salt Lake City, UT 84112, USA
* Author to whom correspondence should be addressed.
Received: 13 December 2012; in revised form: 17 February 2013 / Accepted: 18 February 2013 / Published: 7 March 2013
Abstract: The role of selenium (Se) supplementation in cancer prevention is controversial; effects often depend on the nutritional status of the subject and on the chemical form in which Se is provided. We used a combination of in vitro and in vivo models to study two unique therapeutic windows for intervention in the process of cutaneous melanomagenisis, and to examine the utility of two different chemical forms of Se for prevention and treatment of melanoma. We studied the effects of Se in vitro on UV-induced oxidative stress in melanocytes, and on apoptosis and cell cycle progression in melanoma cells. In vivo, we used the HGF transgenic mouse model of UV-induced melanoma to demonstrate that topical treatment with l-selenomethionine results in a significant delay in the time required for UV-induced melanoma development, but also increases the rate of growth of those tumors once they appear. In a second mouse model, we found that oral administration of high dose methylseleninic acid significantly decreases the size of human melanoma xenografts. Our findings suggest that modestly elevation of selenium levels in the skin might risk acceleration of growth of incipient tumors. Additionally, certain Se compounds administered at very high doses could have utility for the treatment of fully-malignant tumors or prevention of recurrence.
Keywords: selenium; melanoma; selenomethionine; methylseleninic acid; HGF mouse
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MDPI and ACS Style
Cassidy, P.B.; Fain, H.D.; Cassidy, J.P., Jr.; Tran, S.M.; Moos, P.J.; Boucher, K.M.; Gerads, R.; Florell, S.R.; Grossman, D.; Leachman, S.A. Selenium for the Prevention of Cutaneous Melanoma. Nutrients 2013, 5, 725-749.
Cassidy PB, Fain HD, Cassidy JP, Jr, Tran SM, Moos PJ, Boucher KM, Gerads R, Florell SR, Grossman D, Leachman SA. Selenium for the Prevention of Cutaneous Melanoma. Nutrients. 2013; 5(3):725-749.
Cassidy, Pamela B.; Fain, Heidi D.; Cassidy, James P., Jr.; Tran, Sally M.; Moos, Philip J.; Boucher, Kenneth M.; Gerads, Russell; Florell, Scott R.; Grossman, Douglas; Leachman, Sancy A. 2013. "Selenium for the Prevention of Cutaneous Melanoma." Nutrients 5, no. 3: 725-749.