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Dissertação

Exploring the anticancer properties of colonic metabolites derived from Virgin Olive Oil EVALUATED

Detalhes: Colorectal cancer is among the leading causes of mortality through the world. The Mediterranean diet has shown protective action against CRC due to the intake of different components, being one of the main ones, the virgin olive oil. Hydroxytyrosol (HT), the most important phenolic compound in VOO, is reported to present several biological activities. However, the molecular mechanisms underlying the protective action of HT on CRC are still unclear as well as its effect on cancer stem cell’s subpopulation. The aim of this thesis was to evaluate the effect hydroxytyrosol and its colonic metabolites, namely phenyl (PA and PPA) in inhibiting proliferation and targeting cancer stemness on a 3D cell model of CRC - HT29 cell spheroids. Results showed that HT presented the highest antiproliferative effect in both monolayers (EC50=93.58 µM) and spheroids (EC50=3938µM) of HT29 cells. Additionally, HT was the only compound capable of targeting cancer stemness by reducing ALDH+ cells (reduction of 39% for 600µM) and totally inhibiting colony formation at concentrations above 50µM. For the same concentrations tested, PA and PPA showed no significant effect. Gene expression analysis revealed that HT at 200µM slight reduced the expression of markers related to stemness (NANOG, OCT4), Epithelial to Mesenchymal Transition (VIM, TGFβ1), Sonic Hedgehog Pathway (GLI1, PTCH1) and proliferation (CCNA2). This research work shows great promise in developing new and better ways of tackling colorectal cancer treatment, focusing not only on targeting normal cancer cells, but also cancer stem cells resorting to olive oil bioactive compounds.
Keywords: células estaminais cancerígenas, cancro colorrectal, hidroxitirosol, azeite virgem, modelo celular 3D

Discussão: dezembro 9, 2019, 16:0