Carcinogenesis Advance Access published online on February 28, 2008
Carcinogenesis, doi:10.1093/carcin/bgn007
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Superior in vivo inhibitory efficacy of methylseleninic acid against human prostate cancer over selenomethionine or selenite
1 Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912
2 USDA-ARS, Grand Forks Human Nutrition Research Center, P.O. Box 9034, Grand Forks, ND 58202
3 Corresponding author. Dr. Junxuan Lü, Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912. E-mail: jlu{at}hi.umn.edu. Phone 507-437-9680 Fax 507-437-9606
Methylselenol has been implicated as an active anti-cancer selenium metabolite. However, its in vivo efficacy against prostate cancer has yet to be established. Here, we evaluated the growth inhibitory effects of two presumed methylselenol precursors methylseleninic acid (MSeA) and Se-methylselenocysteine (MSeC) in comparison with selenomethionine (SeMet) and selenite in DU145 and PC-3 human prostate cancer xenografts in athymic nude mice. Each selenium was given by a daily single oral dose regimen starting the day after the subcutaneous inoculation of cancer cells. We analyzed serum, liver and tumor selenium content to confirm supplementation status and apoptosis indices and tumor microvessel density for association with anti-tumor efficacy. Furthermore, we analyzed lymphocyte DNA integrity to detect genotoxic effect of selenium treatments. The data show that MSeA and MSeC exerted a dose-dependent inhibition of DU145 xenograft growth and both were more potent than SeMet and selenite, in spite of less tumor selenium retention than in the SeMet-treated mice. Selenite treatment increased DNA single strand breaks in peripheral lymphocytes, whereas the other selenium forms did not. TUNEL and cleaved caspase-3 indices (apoptosis) from MSeC-treated tumors were higher than tumors from control mice or MSeA-treated mice, whereas the microvessel density index was lower in tumors from MSeA-treated mice. In the PC-3 xenograft model, only MSeA was growth inhibitory at a dose of 3 mg/kg body weight. In summary, our data demonstrated superior in vivo growth inhibitory efficacy of MSeA over SeMet and selenite, against two human prostate cancer xenograft models without the genotoxic property of selenite
Key Words: Selenium • methylselenol • prostate cancer • xenograft • athymic nude mice
Received August 27, 2007; revised December 20, 2007; accepted December 21, 2007.
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