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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ongoing Selenium and Vitamin E Chemoprevention Trial is designed to evaluate the efficacy of these two agents, either individually or in combination, in reducing the incidence of prostate cancer in healthy men over 55 years of age. Little information, however, is available on the potential synergy between vitamin E and selenium in chemoprevention. The present study was aimed at addressing this gap of knowledge with the use of the androgen-unresponsive, p53-null, PC-3 human prostate cancer cell line. The growth-inhibitory activity of vitamin E appeared to be dependent on the chemical form. In our hands, D-alpha-tocopheryl succinate (VES) was much more potent than either DL-alpha-tocopherol or D-alpha-tocopheryl acetate. Combining VES with methylseleninic acid (MSA), a selenium metabolite, produced a synergistic effect on cell growth suppression. The synergy was accounted for primarily by an augmented apoptotic response. Poly(ADP-ribose) polymerase cleavage and activation of specific caspases were confirmed by Western blot analysis. The caspases that were commonly modulated by either VES or MSA included initiator caspases-8 and -10, as well as executioner caspases-3, -6, and -7. In contrast, caspase-9 was activated only by VES, whereas caspases-1 and -12 were activated only by MSA. Based on the above information, it is proposed that the mitochondrial pathway and the endoplasmic reticulum stress/cytokine signaling pathway might be involved in apoptosis induction by VES and MSA, respectively. These two pathways may act in a cooperative manner to switch on the full force of the apoptotic machinery when cells are treated with both VES and MSA.
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PMID:Synergy between selenium and vitamin E in apoptosis induction is associated with activation of distinctive initiator caspases in human prostate cancer cells. 1458 1

Methylseleninic acid (MSA) has been shown to have potent anticancer activity and is an excellent compound for studying the anticancer effects of selenium in vitro. To gain insights into the effects of MSA in prostate cancer, we characterized the global transcriptional response of LNCaP, an androgen-sensitive human prostate cancer cell line, to MSA by using high-density cDNA microarrays. We identified 951 genes whose expression shows striking dose- and time-dependent changes in response to 3-30 microM MSA over the time course of 48 h. Transcript levels of many cell cycle-regulated genes change in response to MSA, suggesting that MSA inhibits proliferation. Consistent with these gene expression changes, cell proliferation, monitored by carboxyfluoroscein succinimidyl ester staining, was decreased after MSA treatment, and an accumulation of cells at G0/G1 phase was detected by flow cytometry. Surprisingly, MSA also modulated expression of many androgen-regulated genes, suppressed androgen receptor (AR) expression at both mRNA and protein level, and decreased levels of prostate specific antigen secreted into the medium. Low concentrations of MSA also induced significant increases in transcript levels of phase 2 detoxification enzymes and induced NADPH dehydrogenase, quinone 1 enzymatic activity, a surrogate marker of global phase 2 enzyme activity. Our results suggest that MSA may protect against prostate cancer by inhibiting cell proliferation, by modulating the expression of AR and AR-regulated genes and by inducing carcinogen defenses.
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PMID:Diverse effects of methylseleninic acid on the transcriptional program of human prostate cancer cells. 1461 3

In the planning of future intervention trials using chemopreventive agents against lung cancer, it is critical to evaluate the effect on biomarkers implicated specifically in lung carcinogenesis. With the use of the H520 and H522 human lung cancer cell lines, the present study showed that treatment with selenium (in the form of methylseleninic acid) inhibited cell growth, arrested cell cycle progression at G(1), and induced apoptosis as a late event. Because H520 cells were more sensitive to selenium than H522 cells (IC(50) of MSA was 2.5 or 10 micro M for H520 or H522 cells, respectively, at 24 h), a panel of nine cell cycle regulatory proteins known to be involved in G(1)-->S transition was assessed by Western analysis using whole cell lysate from H520 cells. These nine proteins (DP1, cdc25A, cyclin A, cyclin B(1), cyclin D(1), cdk1, cdk5, p21(WAF1), and GADD153) have been reported previously by our laboratory to be modulated by MSA in human breast and prostate cancer cells. Our data showed that only four (DP1, cdc25A, p21(WAF1), and GADD153) of nine biomarkers produced the expected changes after treatment of lung cancer cells with MSA. This finding raises the possibility that the molecular targets sensitive to selenium modulation may be tissue specific. Thus, the selection of selenium biomarkers for evaluation in an intervention trial must be based on empirical data derived from the cancer cell type of interest.
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PMID:Cell cycle arrest biomarkers in human lung cancer cells after treatment with selenium in culture. 1465 89

Cancer of the prostate is one of the most commonly diagnosed solid malignancies and the fourth leading cause of cancer-related deaths in men living in Italy. With an ageing population, the number of men living with early stages of prostate cancer is expected to increase. There is an impelling need to prevent the onset of the cancer or delay the progression of carcinogenesis in this organ. The chemoprevention of cancer is a relatively new concept defined as the administration of pharmacological agents (drug or diet-derived supplements) to prevent, delay or reverse the carcinogenesis. Epidemiological data showing ethnic and geographic variations in the incidence of, and mortality from, prostate cancer have suggested that the consumption of dietary factors may be protective. There is increasing evidence that diet (particularly dietary fat intake) may play a significant role in early prostate carcinogenesis. Dietary micronutrients and antioxidants are under intense scrutiny. These factors include the vitamin D and E, lycopene, selenium, zinc, poliphenols, isoflavonoids, and phytoestrogens (especially soy products and green tea). The old Mediterranean diet (based on cereals, vegetables, polyunsaturated fats, fruits, fish and low quantities of dairy products and meat) is now sparingly adopted because of the globalisation of the food chain which now involves also our country. Nevertheless, our traditional dietary habits are considered of great value in the prevention of cardiovascular or cancerous diseases and particularly of prostate cancer.
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PMID:[Mediterranean diet, micronutrients and prostate carcinoma: a rationale approach to primary prevention of prostate cancer]. 1466 97

The National Cancer Institute in cooperation with the Southwest Oncology Group has begun one of the largest prostate cancer prevention studies to date, the Selenium and Vitamin E Chemoprevention Trial (SELECT). The purpose of this article is to review the evidence and discuss the individual antioxidant compounds under study. The authors comprehensively reviewed the peer-reviewed literature on the chemoprevention of prostate cancer with emphasis on the antioxidants vitamin E and selenium. The credible leads for the primary prevention of prostate cancer using selenium and vitamin E have emerged as secondary findings from randomized controlled trials with corroborative evidence from observational and in vitro studies. Selenium and vitamin E are widely available compounds that are safe if taken in moderation, with relatively few adverse effects. The evidence in support of the antioxidants in the primary prevention of prostate cancer is promising, and the next step in definitively answering the question has been addressed by the investigators of SELECT. The SELECT study will define the role of the antioxidants selenium and vitamin E in the prevention of prostate cancer; complete data from the study will be available in 12 years.
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PMID:Review of vitamin E and selenium in the prevention of prostate cancer: implications of the selenium and vitamin E chemoprevention trial. 1466 28

A previous controlled intervention trial showed that selenium supplementation was effective in reducing the incidence of prostate cancer. Physiological concentrations of selenium have also been reported to inhibit the growth of human prostate cancer cells in vitro. The present study describes the observation that selenium was able to significantly down-regulate the expression of prostate-specific antigen (PSA) transcript and protein within hours in the androgen-responsive LNCaP cells. Decreases in androgen receptor (AR) transcript and protein followed a similar dose and time response pattern upon exposure to selenium. The reduction of AR and PSA expression by selenium occurred well before any significant change in cell number. With the use of a luciferase reporter construct linked to either the PSA promoter or the androgen responsive element, it was found that selenium inhibited the trans-activating activity of AR in cells transfected with the wild-type AR expression vector. Selenium also suppressed the binding of AR to the androgen responsive element site, as evidenced by electrophoretic mobility shift assay of the AR-androgen responsive element complex. In view of the fact that PSA is a well-accepted prognostic indicator of prostate cancer, an important implication of this study is that a selenium intervention strategy aimed at toning down the amplitude of androgen signaling could be helpful in controlling morbidity of this disease.
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PMID:Prostate specific antigen expression is down-regulated by selenium through disruption of androgen receptor signaling. 1472 1

Vitamin E and selenium are the two most popular dietary supplements used to prevent prostate cancer. The hypothesis that these antioxidants reduce prostate risk is being tested in the selenium and vitamin E chemoprevention trial (SELECT). We hypothesize that selenium potentiates vitamin E-induced inhibition of prostate cancer cell growth in vitro. Prostate cancer cell populations growing asynchronously were treated with a combination of vitamin E and selenium and processed for flow cytometric analysis. Prostate cancer cells treated with a combination of the antioxidants revealed that selenium potentiates vitamin E-induced inhibition of LNCaP cells in vitro. This was demonstrated by a reduction in the percentage of cells in the S phase. This crucial finding confirms our previous observations that antioxidant molecules act via distinct mechanistic pathways. These independent biological effects can be exploited in order to augment the anticancer properties of individual agents. These data also validate the two factorial design of the SELECT trial, permitting pairwise comparisons between agents in combination and alone.
Prostate Cancer Prostatic Dis 2004
PMID:Synergistic effect of vitamin E and selenium in human prostate cancer cell lines. 1474 39

Prostate cancer is the most common cancer diagnosed and the second leading cause of cancer-related deaths in men in the United States. The etiological factors that give rise to prostate cancer are not known. Therefore, it is not possible to develop primary intervention strategies to remove the causative agents from the environment. However, secondary intervention strategies with selenium (Se) compounds and other agents represent a viable option to reduce the morbidity and mortality of prostate cancer. In this review, we discuss ongoing clinical trials. In addition, we discuss preclinical mechanistic studies that provide insights into the biochemical and molecular basis for the anti-carcinogenic activity of both inorganic and organic forms of Se.
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PMID:Chemoprevention of prostate cancer with selenium: an update on current clinical trials and preclinical findings. 1475 76

Epidemiological studies, preclinical investigations and clinical intervention trials support the role of selenium compounds as potent cancer chemopreventive agents; the dose and the form of selenium are critical factors in cancer prevention. Induction of apoptosis and inhibition of cell proliferation are considered important cellular events that can account for the cancer preventive effects of selenium. Toxicity should always be considered a determining factor in the selection of potential chemopreventive agents. Prior to induction of apoptosis, selenium compounds alter the expression and/or activities of a number of cell cycle regulatory proteins, signaling molecules, proteases, mitochondrial associated factors, transcriptional factors, tumor suppressor genes, polyamine and glutathione levels. Depending on the form, selenium compounds can target separate pathways but more efforts are needed to learn about disrupting different pathways converging to apoptosis. Numerous selenium compounds are known to inhibit carcinogenesis in several animal models but not all of these have been examined for their efficacy to induce apoptosis or vice versa in the corresponding target organ. Studies aimed at investigating the effects of selenium compounds on apoptosis in the target organ in vivo and in vitro are limited. On the basis of information provided in this review, we recommend that additional molecular markers should be added to those proposed in the Selenium and Vitamin E Cancer Prevention Trial (SELECT) on prostate cancer. Apart from the selenium compounds reviewed here, several novel synthetic organoselenium compounds need to be examined both in vitro and in vivo for their potential to induce apoptosis; such an investigation may provide better and mechanism-based cancer chemoprevention as well as chemotherapeutic agents.
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PMID:Apoptosis is a critical cellular event in cancer chemoprevention and chemotherapy by selenium compounds. 1496 64

Recent clinical trials have documented that selenium significantly reduces the incidence of clinical prostate cancer. However, nothing is clearly known about the underlying molecular mechanisms by which selenium exerts its anti-cancer effect. This report provides evidence that selenium at micro-molar concentrations induces rapid apoptotic death in human prostate cancer cells, but not in normal prostate epithelial cells. Apoptosis involves activation of caspase 3 which plays a critical role in the cell death process. Interestingly, the apoptosis-inducing effect of selenium in prostate cancer cells is substantially alleviated by the 5-lipoxygenase metabolites, 5(S)-HETE and its dehydrogenated derivative 5-oxoETE, but not by metabolites of 12-lipoxygenase (12(S)-HETE) or 15-lipoxygenase (15(S)-HETE). Apoptosis is also prevented by their precursor, arachidonic acid, an omega-6, polyunsaturated fatty acid, presumably by metabolic conversion through the 5-lipoxygenase pathway. These results indicate that selenium's anticancer effect may involve induction of apoptosis specifically in prostate cancer cells sparing normal prostate epithelial cells, and that 5-lipoxygenase may be a molecular target of selenium's anticancer action. The present report warrants that care should be taken about high intake of dietary fat containing arachidonic acid or its precursor fatty acids when selenium is used for the management of prostate cancer, and suggests that a combination of selenium and 5-lipoxygenase inhibitors may be a more effective regimen for prostate cancer control.
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PMID:Rapid induction of apoptosis in prostate cancer cells by selenium: reversal by metabolites of arachidonate 5-lipoxygenase. 1497 47


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