**3. Cancer and oxidation**

eaten with the this element affect the absorption efficiency of the selenium is said be 'the only

Selenocysteine is a vital component of 35 or more selenoproteins, some of which are important enzymes [22]. Selenium functions as a redox centre, an example of which is the reduction of hydrogen peroxide and lipid and phospholipid hydroperoxides to nondamaging water and alcohols by the glutathione peroxidases [23]. Functions of this kind help maintain membrane integrity, and protect prostacyclin production. Prevention of the oxidative chain reactions in this way prevents further damage to lipids, lipoproteins, and DNA; hence its antioxidant

Selenium deficiency results in impaired immunity [27], and supplementation is immune stimulant. Deficiency increases the virulence of some viruses such as in Keshan disease [28, 29] by altering their genome to a more virulent one. Deficiency may also be associated with low mood [30], increased cognitive decline in older people, and susceptibility to epilepsy [31], exacerbates hypothyroidism in iodine deficiency [32], protective against cardiovascular disease and cancer [33, 34], beneficial in a variety of inflammatory conditions by reducing oxidative stress, and in male fertility [35] through testosterone synthesis and spermatozoa

The conventional cancer therapies currently available are surgery, radiotherapy, and chemo‐ therapy. Chemotherapy is typically the main regimen for most cancers. However, many tumours develop resistance to these harsh drugs, known as chemo resistance, which can lead to other complications [36]. A number of natural products and compounds have been shown to act as effective chemo sensitizers. However, taking antioxidants during cancer treatment could interfere with the way chemotherapy work and diminish their benefits to the patient [37]. It was conclude that the use of supplemental antioxidants during chemotherapy and radiation therapy should be discouraged because of the possibility of tumour protection and reduced survival [37].This is because radiation and some chemotherapy agents work by generating free radicals, which then kill rapidly dividing cancer cells. Since antioxidants scavenge free radicals, they might interfere with the therapeutic effects of these treatments. However, oxidation supports the proliferation of malignant cells and may itself interfere with treatment [38]. People who hold this view maintain that antioxidants may counter the harmful effects of oxidation in the malignant process and thereby increase the effects of drugs or radiation therapy to the benefit of the patient. Moreover, they note that some evidence suggests that antioxidant supplements offer patients protection from the toxic effects of therapy [39]. The balance between oxidants and antioxidants can be a key issue in the development of cancer [40] and reactive oxygen species (ROS) are involved in aging, chronic illness, and cancer. Oxidants also cause free radical damage, thus the body generates large amounts of antioxi‐ dants to prevent harm and maintain health. However, Watson [41] reported that antioxidants can promote cancer growth of late stage metastatic cancers. The process is explained in terms

function helps prevent atheroma and cancer, among other things [24, 25, 26].

trace element to be specified in the genetic code' [21].

296 Pharmacology and Nutritional Intervention in the Treatment of Disease

**2. Clinical applications**

function.

Cancer is a generic term for a large group of diseases that can affect any part of the body and it can exist in many different forms and types, some of which are brought on by the destructive choices people make while others are less predictable and are not the result of destructive decisions. It can be broadly grouped into different types (Carcinomas, Sarcomas, Lymphomas and Leukaemia's), depending on which tissues they come from [43, 44]. Cancer develops when cells multiply in the presence of oxidation and other damage. According to micro-evolutionary models, cells become damaged and change their behaviour, growing uncontrollably, and act like the single-celled organisms from which they originally evolved. The cancer cells' indi‐ vidualism overwhelms the cooperative control processes that are essential to a complex multicellular organism [45, 46]. As cancers become malignant, they exhibit incredible genetic diversity. Whereas a benign tumour is like a colony of similar abnormal cells, a malignant tumour is a whole ecosystem. At this late stage, some (but not all) antioxidants can indeed promote cancer cell growth. Thousands of different cell types coexist: cooperating, competing, and struggling to survive. A consequence of the anaerobic conditions that prevail during the early development of a malignancy is that cancer cells differ from healthy cells, in that they have been selected for the way they generate energy (i.e. anaerobically, using glucose) [47, 48].

The sulfhydryl group is the most sensitive to the oxidizing effects of ROS among the amino acid side chains in protein; it is often involved in the intracellular transduction machinery of redox signals in response to physiological and oxidative stimuli. In fact, a variety of biological functions, not directly related to peroxidase activity, have also been reported for the Prx family [49]. Oxidative damage in DNA can cause cancer. Several antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione Stransferase etc. protect DNA from oxidative stress. It has been proposed that polymorphisms in these enzymes are associated with DNA damage and subsequently the individual's risk of cancer susceptibility [50].

Nutrition and physical activity and major lifestyle changes can reduce the risk of cancer [51, 52]. Antioxidants are becoming an increasingly common choice as a hopeful cancer prevention agent. Importantly, antioxidants limit oxidative damage and thus inhibit early benign cancer growth, preventing cancer from developing. Selenium has received publicity over the past decades based on some confusing and contradictory research about whether low-selenium diets are implicated in cancer risk. To date, this is still a question without a clear answer. However, selenium is required for the proper activity of a group of enzymes collectively called glutathione peroxidase. Each of these enzymes helps to turn toxic hydrogen peroxide into harmless water. Of the eight known glutathione peroxidase enzymes, five of them require selenium. It is a necessary component for appropriate function of the immune system, muscle function, successful reproduction, and peak brain function. Also, selenium produces valuable antioxidant enzymes. Deficiencies in selenium have been linked to decreased thyroid function, cardiovascular disease, and cancers [24]. Research shows selenium, especially when used in conjunction with vitamin C, vitamin E and beta-carotene, works to block chemical reactions that create free radicals in the body (which can damage DNA and cause degenerative change in cells, leading to cancer). Also research has demonstrated that selenium is also linked to reduction in risk to some carcinomas [6, 7].

technologies like immunohistochemistry, flow cytometry, and molecular biologic ap‐ proaches to cancer diagnosis. Cancer is not a singular, specific disease but a group of

The Pharmacology and Biochemistry of Selenium in Cancer

http://dx.doi.org/10.5772/58425

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The biochemistry of selenium differs from other dietary minerals and trace elements. Selenium is not a structural component nor a metal coordination complex and the biosynthesis of selenocysteine is regulated by four genes and begins with the aminoacylation of the amino acid serine by the enzyme serine synthetase to produce Ser-tRNASec [62, 63]. However, selenocysteine is the active site in which, at physiological pH, selenium is fully ionized and is a very efficient redox catalyst [64]. Selenium exists in elemental, organic, and inorganic forms, with four important oxidation states: selenide (Se 2−), elemental (Se0) selenite (Se+4), and selenate (Se+6) [62, 65]. Selenium compounds inhibit signaling enzymes such as protein kinase C (PKC) [66] that play crucial roles in tumor promotion. The selenium-containing nutrient, selenomethionine has been shown to regulate the tumor suppresser p53 by the redox factor refl-dependent redox mechanism. Studies continue to support evidence that one important pathway is that many selenium-containing nutrients can be converted in the body to methyl‐ selenol. Methylselenol has been shown to block expansion of pre-malignant cells forming into fully developed cancers [67]. Several pathways have been proposed that could explain how selenium-containing compounds could block mutated cells from progressing to cancer. Methylseleninic acid has been shown to inhibit NF-kappa B and regulate I kappa B in prostate cancer cells [68]. Selenium compounds inhibit signaling enzymes such as protein kinase C (PKC) [66] that play crucial roles in tumor promotion. A representative of the hydrogen selenide metabolic pool has been found to protect liver cells against damage to DNA. The cellular redox-milieu involves several metabolic, antioxidative and regulatory aspects that are maintained and regulated largely by two enzyme-based systems: the glutathione and thiore‐ doxin systems [69] The thioredoxin and glutathione systems constitute a balanced redox network. The thioredoxin system may influence virtually all phases of tumorgenesis via its

There are several possible mechanisms for the protective effect of selenium. Selenium activates an enzyme in the body called glutathione peroxidase that protects against the formation of free radicals—those loose molecular cannons that can damage DNA. There appear to be at least two distinct families of selenium-containing enzymes [70, 71]. The first includes gluta‐ thione peroxidases Bermano et al [72] and thioredoxin reductase [73], which are involved in controlling tissue concentrations of highly reactive oxygen-containing metabolites. These metabolites are essential at low concentrations for maintaining cell-mediated immunity

The role of selenium in the cytosolic enzyme glutathione peroxidase (GPx) was first illustrated [74, 75]. During stress, infection, or tissue injury, selenoenzymes may protect against the damaging effects of hydrogen peroxide or oxygen-rich free radicals. This family of enzymes

variable tissue responses that result in uncontrolled cell growth [56].

**5. Selenium mechanism**

involvement in transcription and translation [69].

against infections but highly toxic if produced in excess.
