Sialyation In Cancer

In vitro: Daun02 was found to be a good substrate for β-gal, while gal-DCN4 was a poor substrate. Compared with mock-transduced control cells, except for PC3, the β-gal-transduced tumors showed 3- to 60-fold increased sensitivity to Daun02. In addition, in culture medium containing β-gal-transduced cell lines but not in the medium from mock-transduced controls, daunomycin was formed from Daun02 [1].

Treating cells with 0.1mg/ml of 200W sonicated pectin led to 82.82% viable cells, 3.95% early apoptotic cells and 9.84% late apoptotic cells, and according to Fig. 5e, treatment with 0.5mg/ml of 200W sonicated pectin led to reduction of viable cells 56.09%, early apoptosis increased to 14.32 and late apoptosis was 25.18%. The differences between untreated cells and treated cells were all significant (p < 0.05). From the results induction of apoptosis could be linked to pectin concentration, neutral sugar composition, galacturonic acid content and molecular weight, with low molecular weight pectin seemingly more potent than low molecular weight and the higher galactose and galacturonic acid content the higher the activity. The 400W treated pectin had low molecular weight and higher proportion of galactose compared to 200W sonicated

As discussed, galectin-8 is has different functions such as cell growth and apoptosis. When galectin-8 interacts with different integrins, high affinity interactions are formed. When galectin-8 is soluble, it inhibits the cell cycle and prompts the arrest of cell growth [6]. This is caused by a 4-5-fold increase in p21, which is a cyclin-dependent kinase inhibitor [6]. An increase in c-Junc-n-terminal kinases (JNK) and protein kinase B (PKB) activities cause an increase in the levels of p21. When galectin-8 cDNA is transfected into cells of human lung carcinoma, the inhibition of colon formation is noticed; this suggests that when galectin-8 is overexpressed, it may inhibit cell growth [6]. An experiment was done to examine the effects of galectin-8. There were multiple procedures that took place in this experiment; the generation of antibodies against galectin-8, the creation of cell cultures with human carcinoma cells, generation of GFP-galectin-8, generation of GHO cells overexpressing a mutant form of SEK1, the preparation of cell extracts, the binding of galectin-8 to Lactosyl-Agarose beads, Thymidine incorporation, apoptosis, PCR, and a Northern Blot Analysis.

The expression of galectin-8 is found in many different types of tumors [4]. Galectin-8 is found in a lot of prostate-related tumors. For example there are high secretions of it in human prostate carcinoma, early prostate cancer, and prostatic intraepithelial neoplasia; galectin-8 is not found on a normal prostate or in benign prostatic tissues [3]. In addition to prostate-related cancers, galectin-8 was also found in high-levels on human lung carcinoma cells, in central nervous system astrocytoma and glioblastoma, cutaneous T-cell lymphoma, and the middle ear cholesteatoma [3].By quantifying the presence of galectin-8, the malignancy of human colon lung cancer could be diagnosed [5]. “Differential diagnosis is still a prime concern in tumor pathology, and Gal-8 could be of great value in some types of primary and secondary tumors” [4]. In terms of the galectin family, galectin-8 is the most complicated in terms of its expression in cancer and tumor cells and tissues [5]. Further studies and experiments are needed to determine the relevance of galectin-8 in tumors and cancer. In the future, galectin-8 could ultimately be used as a weapon against certain types of cancer

Cancer has become an epidemic across America. About 13 million Americans have cancer and a little over 1 million are diagnosed every year. For years Oncologist have been looking for treatments to cure this horrible disease(American Cancer Society, 2013). Chemistry has such a major impact on the research of cancer. The chemistry within Oncology & Cancer Research has greatly increased our knowledge and capabilities for developing new treatments or actually finding a significant cure (American Cancer Society,2013). This paper is explaining how chemistry is used to seek out cancer cells, treat, and also inform how the different chemicals are affecting our body.

Gaucher disease (GD) is an autosomal recessive inborn error in the pathway of sphingolipid catabolism. Biochemically, this disease is characterized by a deficiency of lysosomal β-glucosidase (glucocerebrosidase GCase, E.C.3.2.1.45) enzyme due to the mutation of GBA gene [1]. The natural substrate of this lysosomal enzyme is glucocerebroside (also called glycosylceramide) mainly present on the cytoplasmic face of cellular membranes and on the cell surface. Lysosomal β-glucosidases play a key role in recycling of this substrate by degradation of glucospingolipid from membranes of apoptatic white blood cells and senescent red blood cells. Genetic mutations of GBA gene affect the enzyme`s catalytic activity and stability and results in the storage

The GM2 activator protein also assists in the transport of the GM2 ganglioside to the lysosome, allowing for further degradation by β-hexosaminidase A. Lysosomes are organelles found in eukaryotic cells that contain important enzymes, such as β-hexosaminidase A, that help to breakdown various substances. Upon reaching the lysosome, the β-subunit of β-hexosaminidase A binds to the GM2 activator protein. The β-subunit of β-hexosaminidase A further activates the α-subunit of β-hexosaminidase A. As a final step in degradation, the α-subunit of β-hexosaminidase A cleaves the terminal N-acetylgalactosamine group from the GM2 ganglioside. This cleavage allows for the GM2 ganglioside to be fully digested by the

In GSH-abundant tissues such as the retina, the most common type of protein oxidation is glutathionylation, which often affects the cysteines on the active sites of proteins and renders proteins dysfunctional (Hoppe et al., 2004). High amounts of PSSG eventually lead to cell injury and death due to the inactivation of multiple important proteins and enzymes (Ghezzi, 2013; Pastore and Piemonte, 2012). Therefore, reversing PSSG is vital to prevent cell damage and death. Specifically, the glutaredoxin family (Grxs) catalyzes the reduction of protein-glutathione mixed disulfides (PSSG) and therefore functions as powerful protein thiol oxidation repair enzymes (Holmgren, 2000; Lillig et al., 2008; Shelton et al., 2005). In mammalian cells, Grxs exist in two subsets: Grx1 and Grx2. Grx1 is primarily localized to the cytoplasm but has been implicated in the nucleus and inner mitochondrial membrane. Concentrated in the mitochondria ten times more than Grx1, Grx2 primarily exerts its protective effects in the mitochondrial matrix but has been associated with the nucleus as well (Gladyshev et al., 2001; Lundberg et al., 2001). Grx1 and Grx2 have a significant Cys-X-X-Cys active site motif. The two cysteine residues act as redox sensors and allow for a monothiol mechanism using the N-terminal cysteine to reduce

siACSL5-PDPA NP transfected U87MG cells and were measured for growth and survival inhibition via Ki67 staining and fluorescence microscopy. Cells transfected with naked siRNA exhibited 55% glioma proliferation as compared to the control group which amassed a 78% proliferation rate (p>0.05), exhibiting the poor efficacy of non-encapsulated siRNA. In contrast, PDPA NP-mediated inhibition of cell proliferation resulted in less than 22% proliferation and five fold inhibition of tumor cell proliferation compared to the control group (Fig. 8; p<0.05).

Glycosylation is the covalent addition of glycans (carbohydrate) to another molecule, which contains a hydroxyl group or other functional group. Other molecule can be proteins, lipids or other bio molecules. This process is a form of co-translational and post-translational modification, which occurs in endoplasmic reticulum (ER) and Golgi apparatus. There are N-linked and O-linked glycosylation processes. In general, this process is involved in cell membrane formation. Further, glycans are located in the glycocalyx. This is a (outer) layer of glycoprotein-polysaccharide on the surface of certain epithelial cells. Glycans participate in many biological processes: cell adhesion, signal transduction, molecular trafficking and clearance, receptor activation and endocytosis. Recent studies have also revealed that glycans are involved in many diseases, from microbial infection to cancer.

When an oligosaccharide chain links to a lipids of a suitable amino acid side chain in proteins, they usually present as glycans, by N- or O-glyosidic bonds. N-linked oligosaccharides are always pentasaccharides attached to asparagine via a beta linkage to the amine nitrogen of the side chain. Alternately, oligosaccharides that are O-linked are commonly attached to threonine or serine on the alcohol group of the side chain. Not all-natural oligosaccharides occur as components of glycoproteins or

The non-enzymatic reaction of reducing sugars with amino groups of amino acids, peptides and proteins is called as non-enzymatic glycosylation or simply glycation. This non-enzymatic reaction ultimately results in the formation of complex brown pigments and protein-protein crosslinks that were first studied under defined conditions by Maillard in the early 1900s (Maillard and Gautier, 1912) and the reaction came to known as the Maillard reaction. There is a condensation reaction between reducing sugar and free amino acids at the amino terminus or susceptible ε-amino group of lysine residues of proteins producing labile N-substituted glycosylamine (Schiff base) that may undergo two sequential rearrangements, forming a stable Amadori product (Fayle & Gerrard, 2002). The reducing sugars namely, glucose, fructose, galactose, mannose, ribose and certain carbohydrate relatives are inherently reactive toward nucleophilic groups. Glucose is the least reactive among common sugars because it exists in least concentration in the open chain form (Paulsen and Pflughaupt, 1980). Amadori rearrangement was a key early step in the Maillard reaction (Hodge, 1955). Early glycation directs the formation of Schiff’s bases and Amadori products that further oxidized to advanced glycated end products (AGEs) (Chetyrkin et al., 2008). Studies have shown that the glycation process (in the early stage where the interaction of sugars, such as glucose, with free amino groups of lysine and

Glycolysis is a major pathway in S. aureus; 85%-90% of the glucose is catabolised through EMP pathway[3, 29]. The very first step of glycolysis is the formation of G-6-P, this is the ubiquitous anabolic intermediate that has essential role in the pathogen from energy generation in the catabolic reactions and upregulation of polysaccharide intracellular adhesion synthesis, virulence factors, cell wall synthesis and formation of SCV are the key characteristic features of drug resistant strains like MDR and VRSA. Polysaccharide intercellular adhesion is a polymer of N-acetyl glucosamine involved in the formation of adhesive exopolysaccharide matrix. This provides structural stability to biofilms, enhanced adhesion to surfaces made protection from host defenses and antibiotics[10, 36]. Majority of G-6-P formation is catalysed by cytoplasmic glk A, this glk A in both Gram positive and Gram negative bacteria comprises of 315-321 residues with a monomeric mass of 33-35 kDa, Km values of glucokinase varied from 0.3-0.8mM for glucose[29]. Glucokinases of bacteria are divided into 2 groups (1) Glucokinases that belongs to ‘Repressor/open reading frames of unknown function/sugar kinases’ (ROK) family which is characterized by the presence of CXCGX(2)GCXE motifs, and (2) Glucokinases without ROK motifs. However, in Archaea two types of ATP-dependent glucokinase are

NetPhos 2.0 analysis projected 9/11/11 serine, 2/3/2 threonine and 5/7/7 tyrosine phosphorylation sites for GS01/GS02/GS03 proteins respectively. The homology modelling of the enzyme shows 12 identical subunits, arranged in two layers of 6. The secondary structure of GS consisted of 7 alpha helix and 15 beta strands. The binding residues, predicted by the RaptorX binding web server, and the corresponding ligands for the three different GS proteins are given in Table 3.

Several parallel beta sheets held together by hydrogen and disulphide bonds create the structure of Polygalacturonase and most enzymes involved in pectin breakdown. Figure 2