Inorganic Selenium Retards Progression of Experimental Hormone Refractory Prostate Cancer

Abstract

The development of hormone refractory prostate cancer marks the onset of the terminal phase of the disease. Despite the use of traditional chemotherapeutic drugs as well as many novel agents life expectancy is not significantly increased beyond palliative care alone. Selenium is a micronutrient that is incorporated into a number of essential enzymes and a minimum intake is necessary for the maintenance of health. In the last few years evidence has accumulated from case-control and limited randomized control data that supranutritional doses of selenium could inhibit the progression of prostate cancer. While much attention has focused on its use as a chemopreventive agent, its use as specific therapy has been limited. We hypothesized that dietary supplementation of selenium would inhibit the progression of hormone refractory prostate cancer in an experimental model. We established orthotopic PC3 tumors in the prostates of 6-week-old male nude mice and fed them a baseline selenium replete diet (0.07 ppm), supplementing intake with different forms of selenium (sodium selenate, selenomethionine, methylselenocysteine and selenized yeast) at 2 different concentrations (0.3 and 3 ppm) in drinking water. Inorganic selenium (sodium selenate) significantly retarded the growth of primary prostatic tumors and the development of retroperitoneal lymph node metastases, which was associated with a decrease in angiogenesis. High dose dietary supplementation of inorganic selenium inhibits the progression of hormone refractory prostate cancer, which is due at least in part to a decrease in angiogenesis.