Tumor establishment and penetration consists of a series of complex processes involving multiple changes in gene expression and protein modification. Proteome changes of tumor tissue were investigated after intraperitoneal administration of a high concentration of ascorbic acid in BALB/C mice implanted with CT-26 cancer cells using two-dimensional gel electrophoresis and mass spectrometry. Eighteen protein spots were identified whose expression was different between control and ascorbic acid treatment groups. In particular, eukaryotic translation initiation factor 3 subunit 1, nucleophosmin, latexin, actin-related protein 2/3 complex subunit 5, M2-type pyruvate kinase, vimentin, tumor protein translationally-controlled 1, RAS oncogene family Ran, plastin 3 precursor, ATPase, Rho GDT dissociation inhibitor β, and proteasome activator subunit 2 expression were quantitatively up-regulated. The increase in the level of these proteins was accompanied by an increase in mRNA level. The cytoskeleton protein actin, vimentin, and tumor protein translationally-controlled 1 showed quantitative expression profile differences. A change in actin cytoskeleton distribution, functionally relevant to the proteome result, was observed after treatment with ascorbic acid. These results suggest a previously undefined role of ascorbic acid in the regulation of cytoskeleton remodeling in tumor tissues.
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Prolonged postprandial hyperglycemia is a detrimental factor for type 2 diabetes and obesity. The benefit of green tea extract (GTE) consumption still requires confirmation. We report the effects of circulating green tea catechins on blood glucose and insulin levels. Oral glucose loading 1 h after GTE ingestion in humans led to higher blood glucose and insulin levels than in control subjects. Gallated catechins were required for these effects, although within the intestinal lumen they have been known to decrease glucose and cholesterol absorption. Treatment with epigallocatechin-3-gallate hindered 2-deoxyglucose uptake into liver, fat, pancreatic beta-cell, and skeletal muscle cell lines. The glucose intolerance was ameliorated by gallated catechin-deficient GTE or GTE mixed with polyethylene glycol, which was used as an inhibitor of intestinal absorption of gallated catechins. These findings may suggest that the gallated catechin when it is in the circulation elevates blood glucose level by blocking normal glucose uptake into the tissues, resulting in secondary hyperinsulinemia, whereas it decreases glucose entry into the circulation when they are inside the intestinal lumen. These findings encourage the development of non-absorbable derivatives of gallated catechins for preventative treatment of type 2 diabetes and obesity, which would specifically induce only the positive luminal effect.
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