gms | German Medical Science

The trace element selenium is an essential component of enzymes which regulate detoxification and repair mechanisms as well as protein synthesis. Selenium has also been linked to prostate cancer (PCA) development. As compared to healthy controls patients with PCA show significantly decreased serum selenium levels. Major reasons are alterations of metabolic processes, sequelae of chemotherapy (CTx) and radiation (RTx), oxidative stress and nutritional habits. CTx and RTx lead to selenium deficiency by a depletion of glutathione peroxidases (GSH-Px). The GSH-Px are selenium dependent key enzymes for the detoxification of reactive oxygen species (ROS). The incidence of PCA correlates strongly to selenium blood levels. Subjects with serum selenium levels > 130 µg/l show a significant risk reduction for PCA. As reported by the representative “VERA study” low selenium intakes (47 µg/d) due to low selenium content in the soil lead to a median serum selenium level of 82.1 µg/l in German men. This value is below the recommended level of 89 µg/l required for GSH-Px saturation levels. Data from large randomized trials (e.g. NPC, SU.VI.MAX, Linxian) suggest an important role of selenium in the development and progression of PCA. The ongoing randomized SELECT study aims at a 25 % PCA risk reduction in 32,000 healthy subjects by supplementation with either selenium (200 µg/d), Vitamin E (400 IE/d) or both vs. placebo. The placebo-controlled “Watchful Waiting Study” randomized subjects with biopsy proven PCA who elected to forgo therapy to either 200 µg/d, 800 µg/d of selenium. Endpoints are time to disease progression and PSA velocity. We present data coming from experimental and clinical studies for a rationale for using selenium as a substance that could effectively decrease the side effects of both CTx and RTx with an enhancement of the efficacy of the antitumor therapy. Inorganic Selenium significantly retarded the growth of hormone refractory prostatic tumors and the development of retroperitoneal lymph node metastases in mice. Selenium inhibits cell growth in PCA cells and enhances the effects of both CTx and RTx on tumor tissues. PSA expression is down-regulated by selenium at physiological doses through disruption of androgen receptor signalling. Recent data show that the anticarcinogenic effects of higher dietary selenium levels are rather related to Methyselenol, a selenium metabolite that selectively promotes apoptosis, inhibits neo-angiogenesis, alters cell cycling and affects gene expression in cancer cells. A toxicity study could demonstrate that biopsy proven PCA patients who received either 1600 µg/d or 3200 µg/d selenium over 1 yr showed no serious side effects and had blood chemistry and haematology results within the normal range. Therefore selenium appears to be an effective supportive agent during standard therapy.