%0 Journal Article
%T PRO-APOPTOTIC EFFECTS OF APPLE PROCYANIDINS IN HUMAN COLON CANCER CELLS AND THEIR DERIVED METASTATIC CELLS EFECTO PRO-APOPT¨®TICO DE PROCIANIDINAS DE MANZANA EN C¨¦LULAS HUMANAS DE C¨¢NCER DE COLON Y SUS C¨¦LULAS METAST¨¢SICAS DERIVADAS
%A Mar¨ªa E MALDONADO C
%A Francis RAUL
%J Vitae
%D 2010
%I Universidad de Antioquia
%X Apples are a rich source of Procyanidins (Pcy) which are able to inhibit colon carcinogenesis in animal models, but the mechanisms through which this occurs are not well understood.The evidence obtained in our laboratory and by other researchers, which shows that Pcy trigger apoptosis through different mechanisms in human colon adenocarcinoma SW480 cells and their derived-metastatic SW620 cells is reviewed in this paper. In the apoptosis induced by Pcy, the polyamine metabolism is involved, but it is not present in SW480 cells. There is a differential sensitivity of both cells lines to the activation of TRAIL-death receptors. Pcy enhance the sensitivity of SW480 cells to TRAIL by activating the extrinsic apoptotic pathway, and overcome TRAIL-resistance in SW620 cells involving a cross-talk between the extrinsic and intrinsic pathways; and a Pcy-induced ROS production favoring mitochondria disruption. In addition, Pcy activate Fas receptor in SW480 cells, whereas SW620 cells are Fas-resistant despite the up-regulated Fas expression. Surprisingly, activation of the Fas receptor-mediated apoptosis by Pcy is observed in SW620 cells after inactivation of TRAIL-death receptors, suggesting that Fas-resistant phenotype may be associated with alterations in downstream events between TRAIL-death and Fas receptors. These data highlight the potential interest of apple Pcy in colon cancer prevention and therapy (combination therapy). Las manzanas son fuente rica en Procianidinas (Pcy), inhiben la carcinog¨¦nesis del colon en modelos animales aunque los mecanismos no son bien comprendidos. Esta revisi¨®n presenta evidencia sobre los efectos pro-apopt¨®ticos de Pcy por diferentes mecanismos en c¨¦lulas humanas de adenocarcinoma de colon SW480 y sus derivadas metast¨¢ticas SW620. En la apoptosis inducida por Pcy en c¨¦lulas SW620 participa el metabolismo de poliaminas, pero no en c¨¦lulas SW480. Existe sensibilidad diferencial de ambas l¨ªneas a la activaci¨®n de los receptores de muerte-TRAIL. Pcy aumenta la sensibilidad de SW480 a TRAIL activando la v¨ªa extr¨ªnseca, y sobrepasa la resistencia a TRAIL en c¨¦lulas SW620 mediante interacci¨®n entre las v¨ªas extr¨ªnseca e intr¨ªnseca, y producci¨®n de especies reactivas del ox¨ªgeno (ROS) con da o mitocondrial. Pcy activan el receptor Fas en c¨¦lulas SW480, mientras que las c¨¦lulas SW620 son Fas-resistentes a pesar del aumento en la expresi¨®n de Fas. La activaci¨®n de la apoptosis v¨ªa Fas por Pcy se observa en c¨¦lulas SW620 despu¨¦s de inactivar los receptores de muerte-TRAIL, sugiriendo que el fenotipo Fas-resistente podr¨ªa estar asociado
%K apoptosis
%K c¨¢ncer de colon
%K flavonoides
%K TRAIL
%K Fas
%K apoptosis
%K colon cancer
%K flavonoids
%K TRAIL
%K Fas
%U http://www.scielo.org.co/scielo.php?script=sci_arttext&pid=S0121-40042010000300012