Ation, it may be hypothesized that the disease progression or response
Ation, it may be hypothesized that the disease progression or response to treatment may highly rely on patient’s individual ability to scavenge either lipid peroxidation products or rePD98059 solubility active species that lead to lipid oxidation (like hydroxyl radical). The interesting issue to be explored under this approach is whether genetic susceptibility associated with antioxidant system, may modify the prooxidative effects in breast cancer subjects. It is well known, that some genetic variations present in the antioxidant enzymes modify their activity or function, which may result in the altered ability to scavenge ROS [6]. These alterations explain some associations between specific gene variants and breast cancer risk [7?1], suggesting protective role of variants linked to the increased antioxidant protection. However, when the tumor is already developed, upregulated antioxidant system may act in an opposite way, promoting cancer cells growth and metastasis [12]. One may hypothesize that genetically determined high ability to scavenge reactive species and especially lipid peroxidation products, may serve as a negative prognostic factor in breast cancer subjects. Natural antioxidant defense consists of many enzymatic and nonenzymatic systems that act in concert withdietary antioxidants [12]. Most important antioxidant enzymes include superoxide dismutases (SOD), glutathione peroxidases (GPx) and catalase (Cat). SOD (including 3 forms: cytosolic – SOD1, mitochondrial – SOD2 and extracellular – SOD3) catalyze dismutation of superoxide anion into hydrogen peroxide, whereas Cat and GPxs reduce hydrogen peroxide, thus preventing production of highly toxic hydroxyl radical [13]. Importantly, GPxs may also reduce hydroperoxides of polyunsaturated fatty acids, counteracting toxic effects of lipid peroxidation. Nonenzymatic endogenous antioxidants (apart from thiols) include metal-binding proteins which sequester prooxidant metals such as iron and copper [12]. One of the important metal-binding proteins is ceruloplasmin (Cp). This enzymatic protein binds copper ions (reducing their deleterious effects) and protects membrane lipids from iron-dependent lipid peroxidation due to its ferroxidase-type activity [13]. Endogenous antioxidant system is supported by exogenous factors derived from diet (like vitamins and trace elements) and the element which probably gained most of scientific interest in terms of its antioxidant properties, is selenium (Se). Many experimental and epidemiological findings suggest significant role of Se in cancer, notably both in PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/25112874 its prevention and promotion, though neither one nor the other mechanism is yet fully understood [14, 15]. It is proposed that Se acts both via low molecular Se compounds and via specific proteins, called selenoproteins. Most of these proteins possess redox activity like for example already mentioned glutathione peroxidases, including GPx1 (cytosolic glutathione peroxidase), GPx2 (gastrointestinal glutathione peroxidase), GPx3 (plasma glutathione peroxidase), GPx4 (phospholipid hydroperoxide glutathione peroxidase) and GPx6 (olfactory glutathione peroxidase) [14]. The activity of GPxs largely depend on Se due to its presence at the active site of these enzymes [16]. There are also other physiologically important selenoproteins, like selenoprotein P (SelP), which is responsible for Se transport or selenoprotein 15 kDa (Sep15), which is involved in protein folding in endoplasmic reticulum [14]. The aim of this.