Antitumoral actions of natural stilbenes derived from Vitis vinifera

Autor: Aja Pérez, Iris
Přispěvatelé: Unité de Recherche Oenologie [Villenave d'Ornon], Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB)-Institut des Sciences de la Vigne et du Vin (ISVV), Université de Bordeaux, Universidad del País Vasco. Facultad de ciencias, Tristan Richard, José Ignacio Ruiz Sanz, Richard, Tristán, Ruiz Sanz, José Ignacio
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Cellular Biology. Université de Bordeaux; Universidad del País Vasco. Facultad de ciencias, 2020. English. ⟨NNT : 2020BORD0115⟩
Addi. Archivo Digital para la Docencia y la Investigación
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Addi: Archivo Digital para la Docencia y la Investigación
Universidad del País Vasco
Popis: The main objective of this Doctoral Thesis is to study the potential anti-inflammatory and anti-tumor activity of resveratrol and other stilbenes present in Vitis vinifera. To achieve this goal, the anti-inflammatory effect of stilbenes is firstly addressed in a lipopolysaccharide (LPS) -activated murine macrophage model, and secondly, antitumor activity in a model of human hepatocarcinoma is analyzed.The stilbenes used for the analysis of antitumor activity comprise 8 monomers (resveratrol, piceide, piceatannol, astringin A, pterostilbene, oxyresveratrol, isorhapontine and isorhapontigenine), 7 dimers (e-viniferin, w-viniferin, d-viniferin, ampelopsin A escirpusin A, pallidol and vitisinol C), a trimer (miyabenol C) and 4 tetramers (hopeaphenol, isohopeaphenol, R2-viniferin and R-viniferin). All were tested in the LPS-activated murine macrophage line, analyzing both their cytotoxicity and their ability to inhibit NO production. From these experiments, their IC30 or IC50, respectively, were calculated. The stilbenes selected based on the results obtained were piceatanol, e-viniferin, δ-viniferin, hopeaphenol and isohopeaphenol, with which the effect that they exert on the release of inflammatory cytokines and the production of ROS was studied. Hopeaphenol and piceatannol inhibit ROS production, and only δ-viniferin does not decrease the release of cytokines IL-1β and TNF-α. It is concluded that the derivatives of resveratrol piceatanol, -viniferin, hopeaphenol and isohopeaphenol have interesting effects on the inflammatory response produced by the activation that LPS exerts on murine macrophages. This finding justifies continuing the study in more complex models given its possible usefulness in the treatment of diseases with an inflammatory basis.For the study of antitumor activity, the IC50 obtained after treatment with 6 stilbenes from the 2 hepatoma lines were compared with the line of non-transformed hepatocytes. Resveratrol (monomer), ampelopsin A and e-viniferin (dimers) and the tetramers hopeaphenol, isohopeaphenol, R2-viniferin and R-viniferin were analyzed. The R2-viniferin tetramer shows the highest cytotoxic activity in HepG2 (IC50
Databáze: OpenAIRE