Cancer is one of the leading causes of death in countries throughout the world. Increase in the production of Reactive Oxygen Species (ROS) has been implicated in many human disease processes, including aging and carcinogenesis. Detoxification of ROS in the cell is provided by both enzymatic and non-enzymatic systems, which constitute the antioxidant defence systems and is crucial to the survival of organisms. The cancer inhibitory propierties of antioxidant compounds such as polyphenols have been well established in experimental and epidemiological studies, showing the intake of these antioxidants within our diet can carry out an effective protective action toward the oxidative stress created in the body by imbalance between ROS and its endogenous defence mechanism. However, the molecular mechanisms responsibles for these effects are not so well known and more studies are needed to provide clear evidence of their protective effects.The aim of this study is to determine and compare the posible antitumoral properties of several polyphenolic fractions, obtained from the extraction and fractionation of wine by-products consisting of grape skins, seeds and stems. These polyphenolic fractions have high antiradical potential and are mainly composed by flavanol monomers with or without gallate groups, glycosylated flavonols and mostly procyanidin oligomers. The effect of these fractions is analysed on cancer cells at cellular and metabolic levels. Moreover, as solar radiation in the UV range is the major source of adverse reactions in the skin and is one of the most efficient environmental carcinogen known, the possible capacity of these fractions to protect against cellular damage induced by ultraviolet radiation is evaluated and compared. The results obtained in this study let us to confirm the polyphenolic fractions studied are very specific antiproliferative agents with very low cytotoxicity to non-proliferative normal cells, such as peripherial blood lymphocites (PBLs). Moreover, treatment with these fractions results in intracellular metabolic changes, restricting the ability of tumoral cells to proliferate and inhibiting glycolysis, being higher for the fraction rich in ECG containing oligomeric flavanols.Like for the study of antitumoral effect at cellular and metabolic levels, the results obtained in the analysis of the protective capacity of these polyphenolic fractions against UV-induced damage, confirm them as potential natural chemopreventive agents. Briefly, the results obtained in this study let us to conclude the polyphenolic fractions rich in procyanidin oligomers and gallate esters are the most efficient as antitumoral agents, active at both cellular and metabolic levels with low cytotoxicity. Additionally, polymerization and percentge of galloylation are also important in the efficacy of the polyphenolic fractions as protectors against damage induced by ultraviolet radiation, suggesting they may be useful for the prevention and treatment of a variety of solar UV light-induced human skin disorders.
| Identifer | oai:union.ndltd.org:TDX_UB/oai:www.tdx.cat:10803/989 |
| Date | 13 January 2006 |
| Creators | Matito Sánchez, Cecilia |
| Contributors | Torres Simón, Josep Lluís, Cascante i Serratosa, Marta, Universitat de Barcelona. Departament de Bioquímica i Biologia Molecular (Biologia) |
| Publisher | Universitat de Barcelona |
| Source Sets | Universitat de Barcelona |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/doctoralThesis, info:eu-repo/semantics/publishedVersion |
| Format | application/pdf |
| Source | TDX (Tesis Doctorals en Xarxa) |
| Rights | info:eu-repo/semantics/openAccess, ADVERTIMENT. L'accés als continguts d'aquesta tesi doctoral i la seva utilització ha de respectar els drets de la persona autora. Pot ser utilitzada per a consulta o estudi personal, així com en activitats o materials d'investigació i docència en els termes establerts a l'art. 32 del Text Refós de la Llei de Propietat Intel·lectual (RDL 1/1996). Per altres utilitzacions es requereix l'autorització prèvia i expressa de la persona autora. En qualsevol cas, en la utilització dels seus continguts caldrà indicar de forma clara el nom i cognoms de la persona autora i el títol de la tesi doctoral. No s'autoritza la seva reproducció o altres formes d'explotació efectuades amb finalitats de lucre ni la seva comunicació pública des d'un lloc aliè al servei TDX. Tampoc s'autoritza la presentació del seu contingut en una finestra o marc aliè a TDX (framing). Aquesta reserva de drets afecta tant als continguts de la tesi com als seus resums i índexs. |
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