title: Dietary flavanols exert different effects on antioxidant defenses and apoptosis/proliferation in Caco-2 and SW480 colon cancer cells.
abstract: Flavanols intake has been associated with reduced risk of cancer. In this study, the anticarcinogenic effects of the flavanols epicatechin (EC), epicatechin-gallate (ECG) and procyanidin B2 (PB2) on Caco-2 and SW480 colon cancer cells were investigated. Catechins showed different cytotoxicity depending on the cell line. ECG displayed strong growth inhibitory effects against SW480 cells, but was ineffective on Caco-2 cells. In contrast, PB2 did not affect Caco-2 cells, whereas promoted cell growth in SW480 cells and EC had no obvious effects on any cell line. Exposure of SW480 cells to ECG led to apoptosis as determined by caspase-3 activity, imbalance among Bcl-2 anti- and pro-apoptotic protein levels, ERK activation and AKT inhibition, whereas PB2 treatment enhanced phospho-AKT and phospho-ERK levels. Incubation of Caco-2 cells with ECG increased glutathione levels without affecting the expression of pro- and anti-apoptotic Bcl-2 proteins, AKT or ERK. The results suggest that the different cytotoxicity of flavanols is caused by their different activity and the degree of differentiation of the colon cancer cell line. Thus, ECG induced apoptosis in SW480 cells and contributed to the cytotoxic effect, whereas ECG enhanced the antioxidant potential in Caco-2 cells. PB2 activated cell proliferation and survival/proliferation pathways in SW480 cells.
authors.affiliation: Department of Metabolism and Nutrition, Instituto de Ciencia y Tecnología de Alimentos y Nutrición (ICTAN, Former Instituto del Frío), Consejo Superior de Investigaciones Científicas (CSIC), José Antonio Novais 10, Ciudad Universitaria, 28040 Madrid, Spain. s.ramos@ictan.csic.es
authors.forename: Sonia
authors.initials: S
authors.lastname: Ramos
authors.forename: Ildefonso
authors.initials: I
authors.lastname: Rodríguez-Ramiro
authors.forename: María Angeles
authors.initials: MA
authors.lastname: Martín
authors.forename: Luis
authors.initials: L
authors.lastname: Goya
authors.forename: Laura
authors.initials: L
authors.lastname: Bravo
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018938:Caco-2 Cells; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000378:metabolism*; D004032:Diet; D005419:Flavonoids / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005419:Flavonoids; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D005978:Glutathione