Life Extension Update Exclusive
Prostate cancer grows more rapidly in selenoprotein deficient mice
In a study published in the online early edition of the Proceedings of the National Academy of Sciences on May 11, 2006, scientists at the University of Illinois in Chicago report their finding that mice bred to develop prostate cancer cross-bred with mice engineered to have reduced selenoprotein levels experienced more rapid development of prostate cancer than control mice bred only to develop prostate cancer. Selenoproteins consist of 25 proteins in the body, such as glutathione peroxidase-1 that contain selenocysteine, Prospective studies have found an association between higher serum or toenail selenium levels and a lower risk of prostate cancer.
For the current study, the prostate glands of the cross-bred mice and those of control mice were examined at 12, 20, 32 and 42 weeks. Progression of hyperplasia, low-grade prostatic intraepithelial neoplasia (or PIN, a precancerous condition), high-grade prostatic intraepithelial neoplasia, and microinvasion were observed. At every time point, the decrease in prostate selenoproteins was associated with an acceleration of prostate cancer development. At 12 weeks, the incidence of high and low grade prostate intraepithelial neoplasia was 70 and 10 percent in the mice with reduced selenoproteins, compared to 35 and 6 percent in the control mice. At 20 weeks, the incidence of high and low grade PIN was equal among the controls, but had progressed to a greater proportion of high-grade lesions in the selenoprotein deficient mice. At 32 weeks, all of the selenoprotein-deficient mice had atypical nuclear lesions, and 46 percent had invasive lesions compared to 15 percent of the controls. By 42 weeks, there were no statistical differences between the groups.
“These data provide evidence for a role of selenoproteins in cancer risk and development,” the authors write. They suggest the possibility that low selenium status is associated with increased prostate cancer risk because of the reduction of one or more selenoproteins. They note the that Nutritional Prevention of Cancer trial results found that selenium supplementation was significant only among individuals whose baseline levels of the trace mineral were lowest, indicating that “selenium supplementation may serve to return reduced levels of selenoproteins to baseline levels required to maximize their benefits.” Alterations in the genes of two selenoproteins may increase the need for higher selenium levels to obtain baseline levels of the selenoproteins, and affect cancer risk. Future studies involving selenium supplementation to selenoprotein deficient mice will help confirm the authors’ hypothesis.
Prostate cancer overview
Measures to prevent PC must be a routine part of the counsel that general practitioners and internists give their patients. Selenium intake of at least 200 mcg a day should be a consideration in the prevention of PC. Low plasma selenium is associated with a four- to fivefold increased risk of PC. In addition, levels of plasma selenium also decrease with age, resulting in middle-aged to older men being at a higher risk for low selenium levels. Ideally, baseline levels of selenium should be obtained before beginning routine selenium supplementation. It would make sense to begin such a micronutrient and mineral assessment at age 25 and perhaps every 10 years thereafter.
The studies of selenium supplementation and its role in preventing PC need continued clarification. In one study, selenium supplements provided benefit only for those individuals who had lower baseline plasma selenium levels. Other subjects with normal or higher levels did not benefit and had a slightly increased risk for PC. The studies by Clark et al. showed that selenium reduced the incidence of PC in men 63%. The mechanism of selenium anti-PC activity appears related to selenium's antiproliferative effect against PC. Selenium affects the cell cycle (see Figure 3) with up-regulation of cell-cycle regulators such as p21 and p27, resulting in a decrease in PC growth due to G1 arrest and up to an 80% reduction in the S-phase of PC growth.
Selenium also has been shown to have a significant antineoplastic effect on breast, lung, liver, and small intestinal tumor cells. Supplementation with selenium enhanced the chemotherapeutic effects of Taxol (paclitaxel) and Adriamycin (doxorubicin) in these cells beyond that seen when the chemotherapeutic drugs were used alone. In studies of the PC cell lines LNCaP and PC-3, the addition of Taxol or Adriamycin, in combination with selenium, caused small but significant inhibition of the PC cell growth. In the cited studies, the optimal inhibition of tumor growth occurred when the plasma selenium level was between 4 -40 ng/mL after 72 hours of treatment.
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