QUERCETIN INDUCES CELL DEATH OF COLORECTAL CANCER CELLS OVEREXPRESSING RAC3

SOARES MACHADO M; PALMA A; LIRA MC; ROSA FD; MARINO G; RUBIO MF; COSTAS MA

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Congreso; REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIA 2020; 2020

Sociedad Argentina de Investigación Clínica

Cancer Stem Cells (CSC) are the responsible of colorectal cancer(CRC) persistence. We have previously demonstrated that RAC3, atranscription coactivator usually overexpressed in CRC is requiredfor maintaining CSC, with anti-apoptotic and anti-autophagy effect.Moreover, Aloysia polystachya (AP) extracts induce the cell death ofCRC, in vivo and in vitro. Quercetin, an agonist of the AHR, was aflavonoid detected at high level as one of the AP components.In this work, we investigated the effects of quercetin and the probableAHR/CSC/RAC3 relationship in CSC of CRC. The effect of theflavonoid was investigated performing cytotoxicity assays in thehuman CRC HCT116wt cell line (overexpressing RAC3) or shRNA-RAC3 stimulated with different concentrations of quercetin for24h. HEK293 cells (low levels of RAC3) were used as a non-tumoralcontrol. The quercetin pathways and AHR/CSC/RAC3 relationshipwere investigated by bioinformatics studies using public repositorymicroarrays data from the human CRC CaCo-2 cells, CD133+ orCD133− side populations, from rat CRC and from human CRC samplesfrom TCGA, using Xena, ConsensusPathDB and STRING platforms.We found that quercetin induced a significant increased cytotoxicityof HCT116wt respect to shRNA-RAC3 HCT116 and HEK293(p