Estudio nutrigenómico de compuestos polifenólicos del cacao y del café en células tumorales humanas

[eng] NUTRIGENOMIC STUDIES OF COCOA AND COFFEE POLYPHENOLS IN HUMAN TUMOR CELL LINES Nutritional genomics research combines the knowledge areas of molecular biology, genetics and nutrition. Nutrigenomics studies how diet, or compounds from diet are able to modulate gene expression. Diet compounds such as polyphenols are known to produce beneficial effects in human homeostasis. Cocoa and coffee are two polyphenol food sources well studied in nutritional research. The aim of this work was to get further insight in the understanding of the mechanism of action through which cocoa and coffee polyphenols exert their beneficial effect, using three different nutrigenomics approaches. The main conclusions of these nutrigenomic studies are: 1) The interaction between ERα and AhR upon incubation with a polyphenolic cocoa extract leads to CYP1A1 induction in breast cancer cells. The synergy between PCE and non-cytotoxic tamoxifen concentrations opens the possibility for a combination therapy based on polyphenols from cocoa that increased tamoxifen efficacy. 2) The activation of Apolipoprotein AI transcription through Site B in its promoter by cocoa flavanol metabolites is mainly mediated by an increase in HNF-3β, with a significant contribution of Sp1 and NFY, as a mechanism for the protective role of these compounds in cardiovascular diseases. 3) Coffee polyphenols are able to affect cyclin D1 expression in cancer cells through the modulation of STAT5B and ATF-2. The results of this thesis led to three publications in international journals; i) “CYP1A1 is overexpressed upon incubation of breast cancer cells with a polyphenolic cocoa extract” in European Journal of Nutrition ii) “Cocoa flavanol metabolites activate HNF-3β, Sp1 and NFY mediated transcription of Apolipoprotein AI in human cells” in Molecular Nutrition and Food Research iii) “Coffee Polyphenols Change the Expression of STAT5B and ATF-2 Modifying Cyclin D1 Levels in Cancer Cells” in Oxidative Medicine and Cellular Longevity.