Selenium and Vitamin E: Interesting Biology and Dashed Hope

Affiliations of author: Glickman Urological and Kidney Institute, Center for Clinical & Translational Research, and Department of Surgery, Cleveland Clinic Lerner College of Medicine, Cleveland, OH.
Journal of the National Cancer Institute (Impact Factor: 12.58). 03/2009; 101(5):283-5. DOI: 10.1093/jnci/djp009
Source: PubMed
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    • "This concerning finding highlights the importance of understanding the role of ROS in prostate tumorigenesis. In fact, one of the lead authors of the SELECT trial has suggested that any success in future chemoprevention may reside in the identification of specific risk factors in individuals that will help determine the effect any agent may have on their tumor development [20]. "
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    ABSTRACT: Discordant results in preclinical and clinical trials have raised questions over the effectiveness of antioxidants in prostate cancer chemoprevention. Results from the large-scale Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed that antioxidants failed to prevent, and in some cases promoted, prostate cancer formation in men without a history of the disease. One possible explanation for these alarming results is the notion that the effects of antioxidant treatment on the prostate are modified by specific, intrinsic genetic risk factors, causing some men to respond negatively to antioxidant treatment. Loss of expression of the homeobox transcription factor NKX3.1 in the prostate is frequently associated with human prostate cancer. Nkx3.1 mutant mice display prostatic hyperplasia and dysplasia and are used as a model of the early stages of prostate cancer initiation. While the mechanisms by which Nkx3.1 loss promotes prostate tumorigenicity are not completely understood, published data have suggested that elevated reactive oxygen species (ROS) associated with Nkx3.1 loss may be a causative factor. Here we have tested this hypothesis by treating Nkx3.1 mutant mice with the antioxidant N-acetylcysteine (NAC) for 13 weeks post-weaning. Surprisingly, while NAC treatment decreased ROS levels in Nkx3.1 mutant mouse prostates, it failed to reduce prostatic epithelial hyperplasia/dysplasia. Rather, NAC treatment increased epithelial cell proliferation and promoted the expression of a pro-proliferative gene signature. These results show that ROS do not promote proliferation in the Nkx3.1-null prostate, but instead inhibit proliferation, suggesting that antioxidant treatment may encourage prostate epithelial cell proliferation early in prostate tumorigenesis. Our findings provide new insight that may help explain the increased prostate cancer risk observed with vitamin E treatment in the SELECT trial and emphasize the need for preclinical studies using accurate models of cancer.
    PLoS ONE 10/2012; 7(10):e46792. DOI:10.1371/journal.pone.0046792 · 3.23 Impact Factor
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    • "However, their efficacy in vivo remains a matter of debate. Animal models have been widely used to test a number of antioxidant compounds, and though these studies have been relatively promising, clinical trials with antioxidant compounds have not always lived up to expectations (Schwedhelm et al., 2003; Kamat et al., 2008; Klein, 2009; Wojcik et al., 2010; Floyd et al., 2011). One reason why antioxidants have performed poorly in clinical trials might have to do with the fact that these compounds may only be effective in a narrow temporal window in relation to oxidative damage. "
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    ABSTRACT: Oxidative stress remains one of the most well studied, albeit somewhat contentious, causes of age-related changes in humans. Consequently, a large number of putative antioxidant compounds are freely available in myriad formulations that are often not tested for their efficacy or regulated for quality control. Following the development of a Drosophila model of oxidative-stress dependent aging (p38 MAP K (p38K) mutants) in our laboratory, we attempted to test the protective effect of some of these commonly available formulations against oxidative stress, in the p38K model. As environmental exposure to oxidizing toxins has been linked to a variety of human diseases, we also tested the efficacy of these supplements on chemically-induced models of oxidative stress (paraquat and hydrogen peroxide exposure). Our results suggest that when added as a dietary supplement, some of these over-the-counter compounds, notably containing açai extracts, confer significant protection for both the p38K-dependent genetic model as well as the toxin-induced model. These products were also remarkably effective at dampening stress-induced expression of the detoxifying enzyme GSTD1 and eliminating paraquat induced circadian rhythm deficits. Overall, our results suggest potential benefits of dietary supplementation with some of these compounds, especially under conditions of elevated oxidative stress. These findings should be assessed in the context of other studies that seek to identify active principles in these extracts, determine their effective dosage for human consumption and evaluate the safety of long-term prophylactic applications.
    Experimental gerontology 07/2012; 47(9):712-22. DOI:10.1016/j.exger.2012.06.016 · 3.49 Impact Factor
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    • "The presence of eicosane in other plant species was reported, but its activity could not be confirmed (Soma, Kiranmayee, Bhuvaneswari, Archana, & Lakshmi, 2010; Uma & Parvathavarthini, 2010). Vitamin E (26.69% (A)) might not have a role in antimicrobial activity, but is an excellent free radical scavenger involved in the prevention of prostate cancer (Eric, 2009). Oleic acid acts as an anionic surfactant at low pH exhibiting antimicrobial properties (Hayes & Berkovitz, 1979). "
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    ABSTRACT: Gymnema sylvestre (CS 149), known to be a rich source of saponins and other valuable phytochemicals, has been analysed for antimicrobial activity. The chloroform extracts of aerial and root parts of G. sylvestre exhibited higher antimicrobial activity as compared to diethyl ether and acetone. The root extracts of chloroform have shown competitive minimum inhibitory concentration and minimum bactericidal concentration values in the range of 0.04-1.28 mg mL(-1) and 0.08-2.56 mg/mL, respectively, towards the pathogens. The GC-MS analysis of chloroform extracts has shown the presence of compounds like eicosane, oleic acid, stigmasterol and vitamin E.
    Natural product research 04/2012; 27(6). DOI:10.1080/14786419.2012.676548 · 0.92 Impact Factor
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