Scientists Explain How Selenium Affects Cancer

Transcription

1 Scientists Explain How Selenium Affects Cancer

2 2014 Selenium and cancer: A story that should not be forgotten Insights from genomics Catherine Meplan and John Hesketh, Advances in Nutrition and Cancer, Cancer Treatment and Research 159; : V. Zappia et.al, (eds.) low serum selenium was reported to be a pre-diagnostic indicator of higher cancer risk, particularly for gastrointestinal and prostate cancers A subsequent trial in China with a daily 50mcg/day supplement of selenised yeast was found to lower esophageal cancer mortality. several lines of evidence, including reduced activity/expression of some selenoproteins in breast, prostate, colorectal and lung cancers.suggest a role for selenoproteins in the aetiology of cancer initiation and progression. risk of advanced [prostate] cancer is significantly modified by Se status 2013 Does a role for selenium in DNA damage repair explain apparent controversies in its use in chemoprevention? [review] Soumen Bera et.al., Mutagenesis :2: , 2013 Considerable experimental evidence indicates that one possible mechanism by which selenium supplementation may exert its benefits is by enhancing the DNA damage repair response selenium supplementation has been shown to be beneficial in reducing the frequency of DNA adducts and chromosome breaks, consequentially reducing the likelihood of detrimental mutations that ultimately contribute to carcinogenesis. Selenium, therefore, may be protective by preventing DNA damage from occurring as well as by increasing the activity of.dna damage repair pathways The most promising evidence for a benefit of higher selenium intake has come from metaanalyses Two recent meta-analyses have also concluded that selenium supplementation may be useful in the reduction of several cancer types The possible benefits of selenium in humans is supported by an extensive literature of in vitro and animal model systems indicating that low, non-toxic levels of selenium can protect against cancer. The broad efficacy of selenium in this regard is impressive. the list of target organs is extensive and includes skin, prostrate, lung, [breast and colon] etc. Equally extensive is the list of chemical carcinogens that selenium supplementation has been shown to be effective against selenium may be working via multiple mechanisms and at different levels of carcinogenesis. selenium have been shown to effectively reduce tumor incidence in animal models, selectively be toxic to tumor cells in vitro and typically require higher concentrations to achieve their benefits, being well above the doses required to saturate the production of selenoproteins. the mechanisms by which selenium prevents tumor development are likely to be complicated and involve multiple mechanisms that impact distinct phases of carcinogenesis. At supernutritional levels. differential toxicity to tumor cells as compared to normal cells has been documented by several lines of evidence, as well as potential effects of angiogenesis well over 100 independent publications indicating that selenium supplementation of the diets of laboratory animals can reduce the incidence of cancer in carcinogen-exposed rodents. What is particularly striking is the efficacy of selenium in multiple organs and against a wide variety of carcinogens that stimulate carcinogenesis via different mechanisms.

3 Hemodialysed patients are at greater risk of DNA lesions and supplementation of the diets of 42 chronic kidney disease patients with 200mcg selenium...demonstrated a benefit of selenium supplementation One of the most convincing links between selenium and DNA repair has emerged from studies on women who are at increased risk of breast cancer supplementation of [genetic] BRCA1 carriers with 670mcg of selenium in the form of selenite for 103 months returned the levels of [DNA] breaks to that of the non-carriers. there would appear to be multiple mechanisms by which selenium could stimulate DNA repair That selenium can protect against cancer is a foregone conclusion based on a wealth of animal data that has accumulated over decades. Is selenium a potential treatment for cancer metastasis? [review] Yu-Chi Chen, K. Sandeep Prabhu and Andrea M. Mastro; Nutrients 2013;5: [we review] studies indicating that Se compounds and selenoproteins inhibit cell motility, migration, and invasion, and reduced angiogenic factors...and studies showing that Se supplementation resulted in reduced micro-vessel density and metastasis. Together these data support the notion that Se may be an anti-metastastatic element in addition to being a cancer preventative agent. Se supplementation exhibited beneficial effects on lung, bladder, colorectal, oesophageal, gastric cardia and thyroid cancers the literature is replete with reviews that discuss the potential mechanisms through which Se can suppress tumor initiation and primary tumor growth.briefly, Se can affect cancer by regulating the expression of redox-active proteins, modulating the redox status of several proteins, balancing intracellular redox status, regulating inflammatory and immune responses, maintaining DNA stability, inducing cell cycle arrest and apoptosis, inhibiting local invasion and migration, blocking angiogenesis, activating or inactivating crucial regulatory proteins of cell proliferation, and enhancing phase II-carcinogen-detoxifying enzymes. metastasis is often the cause of death in cancer patients Metastasis is a multi-step process that begins with the invasion of tumor cells into adjacent tissue followed by trans-endothelial migration into circulating vessels (intravasation) leading to extravasation into tissues and ending with cell proliferation and subsequent angiogenesis at secondary sites. In this review we will present the current knowledge of how selenium proteins and Se supplementation may affect tumor migration, invasion, angiogenesis, and overall metastasis in breast, prostrate, colon, melanoma, fibrocarcinoma, glioma, skin, liver, and lung cancers. Se stabilized cell structure, reduces cell motility, and limits cell migration and invasion in cell culture. Se impacted both endothelial and cancer cells and lead to the reduction of major regulatory molecules in angiogenesis.confirmed that Se reduced angiogenesis. Se was able to target established tumors. Furthermore, the effect of Se on angiogenesis was rapid. [within a few days] breast cancer migration and invasion were significantly limited by Se in vitro. These changes may hinder the ability of breast cancer to break cellular barriers and initiate metastasis. Angiogenesis was also impaired by the presence of Se. The rapid reduction of microvessel density suggests the possibility of utilizing Se supplementation as an anti-angiogenesis therapy. This greater effect of Se on advances disease, compared to its effect on localized tumors, was also highlighted in the NPC trial and several other studies...indicated that Se is likely to interfere with prostate cancer metastasis

4 GPX3 [glutathione-peroxidase-3] may be a tumor and metastasis suppressor in prostrate cancer. [Se] supplementation significantly reduced tumor volume and microvessel formation [in human colon cancer cells]. Se reduced the expression and activation of angiogenic factors produced by [human fibrosarcoma] cells, which increased the difficulty to the metastasis development. lung carcinoma cells [selenium] alone caused a reduction of lung metastasis by 55% In head and neck squamous cell carcinoma, several reports suggest the effectiveness of [selenium]. The [selenium] treatment significantly reduced the microvessel density and increased vascular maturation, which contributed to the enhanced delivery efficiency and distribution of the anti-cancer drug [selenium] induced apoptosis [programmed cell death] in human astrocytoma [brain cancer] cells the results of many in vitro and animal studies have suggested that Se is a promising chemopreventative and anti-cancer agent. In summary.se has been shown to affect cancer cell migration and invasion, inhibit angiogenesis, promote vascular maturation, enhance drug delivery and distribution, and decreases metastasis. Which form is that? The importance of selenium speciation and metabolism in the prevention and treatment of disease. [review] Claire M. Weekley and Hugh H. Harris, Chemical Society Review,2013; 42, Early trials with selenised yeast at doses up to 800mcg of selenium per day for several years showed no adverse effects. Meta-analyses of observational studies have found that selenium status is inversely associated with lung, bladder and prostate cancers. Selenium compounds may sensitize cancer cells to chemotherapeutic drugs. The nutritional prevention of cancer (NPC) trial.showed that selenium supplementation (200mcg per day as selenised yeast) significantly reduced total cancer mortality, total cancer incidence and the incidence of prostate, lung and colorectal cancers The cytotoxicity and anti-cancer activity of selenium is attributed to its pro-oxidant action. Cancer cells are more sensitive to selenium than normal cells. The GPxs may inhibit initiation of cancer by catalyzing the reduction of GHS of a range of hydroperoxides selenium compounds are capable of binding copper and iron and preventing oxidative DNA damage induced by these metals. it has become apparent that selenite-induced cell death [apoptosis] is mediated via the mitrochondrial pathway. Selenite has been shown to. [cause] apoptosis in a number of cancer cell lines. The sensitivity of cancer cells in general, as well as chemotherapeutic drug-resistant cancer cells, to selenium may be linked to TrxR levels

5 In a study of the sensitivity of lung cancer cell lines towards selenite, the cell lines with the greatest TrxR expression, which also had the greatest resistance to doxorubicin [a chemotherapy] was most sensitive. In malignant mesothelioma cells, selenite was more toxic to the therapyresistant sarcomatoid cells Histone deacetylases (HDAC).due to their aberrant recruitment and overexpression in cancer cell lines, HDCAs are anti-cancer targets. Tumor cells are more sensitive to HDAC inhibitors than normal cells selenium compounds have two mechanisms of HDAC inhibition. Selenium and hypertension: do we need to reconsider selenium supplementation in cancer patients? [correspondence] Oliver Micke et.al., Journal of Hypertension 2013;31:5:1049 There is increasing interest in using selenium for prevention of cancer or other serious diseases or for treatment or prevention of side-effects from an effective oncological therapy. we reported that it was possible to and balance the preexisting selenium deficiency by supplementing 500 mcg sodium selenite per day orally during the 5-6 weeks of radiotherapy. In addition, the supplementation reduced the number of episodes and severity of radiation-associated diarrhea. selenium efficiently reduced some side-effects of the radiation treatment. In the longterm follow-up of more than 5 years, we observed even a small but statistically significant advantage of overall survival in the patient group receiving selenium. The potential benefits [of selenium] for the cancer patient under radiotherapy are well documents and undisputable Effects of mineral supplementation on liver cirrhotic/cancer male patients Tasneen Gul Kazi et.al., Biological Trace Element Research :81-90 Selenium (Se)-assisted enzyme glutathione peroxidase.acts as an antitumor agent. Se also appears to be protective in individuals infected with hepatitis virus (B or C) against the progression of the condition to liver cancer. The low levels of Se in both biological samples of liver cirrhotic/cancer patients indicated the decrease in liver function, resulting in progression of liver cirrhosis. Se compounds comprise hepatoprotective effects against different types of oxidative stress and decrease DNA damage. Thus selenium deficiency may predispose to development of cancers. Se supplementation has protective effects in the development of primary liver cancer and has also been associated with a decreased incidence in cancer in general. 100 mcg pre day of selenium may improve liver function in people with alcoholic cirrhosis Selenium in Breast Cancer Juan-Bosco Lopez-Saez et.al., Oncology 2003;64: Patients whose breast cancer was in complete remission had normal or near-normal levels of selenium. In contrast, the subgroup of women with clinically active disease had the lowest mean level of all subgroups studied. Our results suggest that the decrease in serum concentrations of selenium in women with breast cancer was a consequence rather than a cause of the cancer. Serum Selenium levels in relation to markers of neoplastic progression among persons with Barrett s Esophagus

6 Rebecca E. Rudolph et.al., Journal of National Cancer Institute 2003;95: higher serum selenium levels may be associated with a reduced risk of esophageal adenocarcinoma higher levels of selenium in blood and toenail samples have been associated with a decreased risk of squamous esophageal, gastric, lung, liver, pancreatic and thyroid cancers. selenium has been demonstrated to inhibit the growth of neoplastic [cancer] cells and tissue New concepts in selenium chemoprevention Clement Ip, Yan Dong and Howard E. Ganther, Cancer and Metastasis Reviews 2002;21: we have shown that selenium affects not just one key [anticancer] target, but a multitude of targets. In doing so the impact of selenium is amplified. The diversity of molecular targets also makes it difficult for premalignant cells to escape the inhibitory effect of selenium. Selenium supplementation and lung cancer incidence: an update of the Nutritional Prevention of Cancer Trial Mary E. Reid et.al, Cancer Epidemiology, Biomarkers & Prevention 2002;11; Results from ecologic studies, epidemiological studies, human clinical intervention trials, and in vitro and in vivo animal models clearly support a protective role of selenium against cancer development. It is of particular interest that selenium supplementation appears to have chemoprotective effects in persons with relatively heavy tobacco use histories.thus both current and former smokers may benefit from selenium supplementation The protective role of selenium on genetic damage and on cancer [review] Karam El-Bayoumy, Mutation Research 2001;475: Daily doses of mcg Se inhibited genetic damage and cancer development in humans. Clearly, doses above the RDA are needed to inhibit genetic damage and cancer. the chemopreventative effect of selenium is due in part to its inhibitory effect on cell growth, DNA, RNA, and protein synthesis in transformed cells. early transformed [cancer] cells are sensitive to selenium intervention, whereas normal cells are not. Selenium as a cancer preventative agent; Chapter 17 of Selenium, Its Molecular Biology and Role in Human Health Gerald F. Combs Jr. and Junxuan Lu, Edited by Dolph L. Hatfield, 2001 [and liver cancer] general mechanisms would appear to underlie the anti-carcinogenetic effects described for selenium [include] cellular antioxidant protection, carcinogen metabolism, gene expression, immune surveillance, cell cycle/death regulation and neo-angiogenesis The importance of selenium to human health [review]

7 Margaret P. Rayman, Lancet 2000;356: An elevated selenium intake may be associated with reduced cancer risk. low selenium status was associated with a significantly increased risk of cancer incidence and mortality. The Nutritional Prevention of Cancer Trial.those receiving [200mcg/day] selenium showed.50% lower total cancer mortality and 37% lower total cancer incidence with 63% fewer cancers of the prostate, 58% fewer cancers of the colon and 46% fewer cancers of the lung. Thus the anticancer effect of selenium may relate more closely to its ability to enhance the immune response or, more likely, to its ability to produce anti-tumorgenic metabolites.that can perturb tumor-cell metabolism, inhibit angiogenesis, and induce apoptosis of cancer cells. compiled/edited by Howard S. Armistead, 21 March 2014