title: Selenium for the prevention of cutaneous melanoma.
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.
authors.affiliation: Department of Medicinal Chemistry, Huntsman Cancer Institute, Salt Lake City, UT 84112, USA. Pamela.cassidy@hci.utah.edu
authors.forename: Pamela B
authors.initials: PB
authors.lastname: Cassidy
authors.forename: Heidi D
authors.initials: HD
authors.lastname: Fain
authors.forename: James P
authors.initials: JP
authors.lastname: Cassidy
authors.forename: Sally M
authors.initials: SM
authors.lastname: Tran
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Moos
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Boucher
authors.forename: Russell
authors.initials: R
authors.lastname: Gerads
authors.forename: Scott R
authors.initials: SR
authors.lastname: Florell
authors.forename: Douglas
authors.initials: D
authors.lastname: Grossman
authors.forename: Sancy A
authors.initials: SA
authors.lastname: Leachman
mesh_terms: D000818:Animals; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D019382:Human Growth Hormone / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008545:Melanoma / Q000517:prevention & control*; D051379:Mice; D008822:Mice, Transgenic; D016566:Organoselenium Compounds; D016016:Proportional Hazards Models; D012313:RNA; D012643:Selenium / Q000627:therapeutic use*; D017279:Selenocysteine / Q000031:analogs & derivatives; D012878:Skin Neoplasms / Q000517:prevention & control*; D018038:Sodium Selenite; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D016566:Organoselenium Compounds; D017279:Selenocysteine; D019382:Human Growth Hormone; D012313:RNA; C008493:methylselenic acid; D012643:Selenium; D018038:Sodium Selenite; C002979:selenomethylselenocysteine