Chemoprevention of prostate cancer with selenium: An update on current clinical trials and preclinical findings

Meuillet, Emmanuelle J.; Stratton, Suzanne; Cherukuri, Durga P.; Goulet, Anne Christine; Kagey, Jacob D.; Porterfield, B. W.; Nelson, Mark A.

doi:10.1002/jcb.10728

Cited by 80 publications

(43 citation statements)

References 95 publications

(89 reference statements)

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“…Many potential preventive mechanisms have been proposed for selenium, including direct and indirect effects (21). Selenoproteins may act as antitumorigenic proteins and protect against DNA damage from xenobiotics.…”

Section: Discussionmentioning

confidence: 99%

“…The Selenium and Vitamin E Cancer Prevention Trial and other trials outlined elsewhere (21,41) are addressing important questions of selenium biology, including whether selenium works primarily on subclinical, microscopic cancer or in preventing or reversing preneoplastic lesions. For example, biopsies taken during the course of the Selenium and Vitamin E Cancer Prevention Trial will allow selenium and nonselenium groups to be compared for the secondary end point of prostatic intraepithelial neoplasia.…”

Section: Discussionmentioning

confidence: 99%

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Selenium Accumulation in Prostate Tissue During a Randomized, Controlled Short-term Trial of l-Selenomethionine: a Southwest Oncology Group Study

Sabichi

Lee

Taylor

et al. 2006

Clinical Cancer Research

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Purpose: Epidemiologic and clinical data suggest that selenium could prevent prostate cancer, but it has not been shown that supplemental selenium leads to an increased concentration of selenium in prostate tissue compared with adjacent tissue. Experimental Design: We conducted a randomized, controlled, short-term trial of l-selenomethionine (SeMet) versus observation in men with organ-confined prostate cancer. The primary endpoint was the measurement of selenium concentration in prostate tissue and seminal vesicle (SV).We assessed baseline selenium levels in serum and in toenail specimens (reflecting long-term intake) and post-intervention selenium levels in serum, and in prostate and SV tissues using hydride generation atomic fluorescence spectroscopy. Results: Sixty-six eligible patients were randomly assigned to the SeMet (n = 34) or observation (n = 32) arm; both arms had similar baseline patient characteristics. Baseline serum selenium was similar in the two groups (P = 0.64). Baseline toenail selenium levels were slightly higher in the SeMet group than in the control group (P = 0.07). After the intervention, the mean serum selenium level increased 15% in the SeMet arm and was higher than in the observation arm (P = 0.001). The selenium concentration in prostate tissue was 22% higher in the SeMet arm (n = 26) than in the observation arm (n = 25; 1.80 versus 1.47 ppm; P = 0.003, Wilcoxon rank sum test) and remained significantly higher after adjusting for chronic selenium intake (P = 0.021, ANCOVA). SV selenium concentration was similar in both groups (P = 0.384) and was lower than in prostate tissue. Conclusions: The present study is the first to show that selenium taken as oral supplementation accumulates preferentially in the human prostate gland as opposed to the SV. These findings support the hypothesis that oral selenium supplementation may contribute to the cancer preventive effects of selenium.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Selenium Accumulation in Prostate Tissue During a Randomized, Controlled Short-term Trial of l-Selenomethionine: a Southwest Oncology Group Study

Sabichi

Lee

Taylor

et al. 2006

Clinical Cancer Research

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“…11,12 Selenide is then transformed by methyltransferase into methylselenol (CH 3 SeH) and further methylated metabolites. Additionally, selenide is an intermediate for selenoproteins, Se-sugar, and elemental Se.…”

Section: ■ Introductionmentioning

confidence: 99%

Selenite-Induced Toxicity in Cancer Cells Is Mediated by Metabolic Generation of Endogenous Selenium Nanoparticles

et al. 2015

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Selenite has been a touted cancer chemopreventative agent but generates conflicting outcomes. Multiple mechanisms of selenite cytotoxicity in cancer cells are thought to be induced by metabolites of selenite. We observed that intracellular metabolism of selenite generates endogenous selenium nanoparticles (SeNPs) in cancer cells. Critical proteins that bind with high affinity to elemental selenium during SeNPs self-assembly were identified through proteomics analysis; these include glycolytic enzymes, insoluble tubulin, and heat shock proteins 90 (HSP90). Sequestration of glycolytic enzymes by SeNPs dramatically inhibits ATP generation, which leads to functional and structural disruption of mitochondria. Transcriptome sequencing showed tremendous down-regulation of mitochondrial respiratory NADH dehydrogenase (complex I), cytochrome c oxidase (complex IV), and ATP synthase (complex V) in response to glycolysis-dependent mitochondrial dysfunction. Sequestration of insoluble tubulin led to microtubule depolymerization, altering microtubule dynamics. HSP90 sequestration led to degradation of its downstream effectors via autophagy, ultimately resulting in a cell-signaling switch to apoptosis. Additionally, the surface effects of SeNPs generated oxidative stress, thus contributing to selenite cytotoxicity. Herein, we reveal that the multiple mechanisms of selenite-induced cytotoxicity are caused by endogenous protein-assisted self-assembly of SeNPs and suggest that endogenous SeNPs could potentially be the primary cause of selenite-induced cytotoxicity.

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“…The majority of investigation with selenium has emphasized cancer chemoprevention, and there are a number of large prevention clinical trials, many focusing on prostate cancer (1). The potential role for selenium in cancer chemotherapeutics is an area that has shown significant promise in preclinical and small clinical trials, but this potential has been overshadowed by the prevention studies.…”

Section: Introductionmentioning

confidence: 99%

Chemotherapeutic selectivity conferred by selenium: a role for p53-dependent DNA repair

Fischer

Mihelc

Pollok

et al. 2007

Molecular Cancer Therapeutics

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Selenium in various chemical forms has been the subject of cancer chemoprevention trials, but, more recently, selenium has been used in combination with DNA-damaging chemotherapeutics. Specifically, selenium protected tissues from dose-limiting toxicity and, in fact, allowed delivery of higher chemotherapeutic doses. At the same time, selenium did not protect cancer cells. Therefore, we seek to define the genetic basis for the observed selectivity of selenium in combination chemotherapeutics. The tumor suppressor p53 is mutated in the vast majority of cancers, but is by definition wild-type in nontarget tissues such as bone marrow and gut epithelium, tissues that are often dose-limiting due to DNA damage. We used primary, low-passage mouse embryonic fibroblasts that are wild-type or null for p53 genes to test differential effects of selenium. Seleno-L-methionine, nontoxic by itself, was used to pretreat cell cultures before exposure to UV radiation or UV-mimetic cancer chemotherapy drugs. Seleno-L-methionine pretreatment caused a DNA repair response, which protected from subsequent challenge with DNA-damaging agents. The observed DNA repair response and subsequent DNA damage protection were p53 dependent as neither was observed in p53-null cells. The data suggest that (a) p53 may be an important genetic determinant that distinguishes normal cells from cancer cells, and (b) combinatorial chemotherapeutics that act by p53-dependent mechanisms may enhance chemotherapeutic efficacy by increasing the chemotherapeutic window distinguishing cancer cells from normal cells. [Mol Cancer Ther 2007;6(1):355 -61]

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Chemoprevention of prostate cancer with selenium: An update on current clinical trials and preclinical findings

Cited by 80 publications

References 95 publications

Selenium Accumulation in Prostate Tissue During a Randomized, Controlled Short-term Trial of l-Selenomethionine: a Southwest Oncology Group Study

Selenium Accumulation in Prostate Tissue During a Randomized, Controlled Short-term Trial of l-Selenomethionine: a Southwest Oncology Group Study

Selenite-Induced Toxicity in Cancer Cells Is Mediated by Metabolic Generation of Endogenous Selenium Nanoparticles

Chemotherapeutic selectivity conferred by selenium: a role for p53-dependent DNA repair

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