QUERCETIN INDUCES CELL DEATH OF COLORECTAL CANCER CELLS OVEREXPRESSING RAC3

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

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Congreso; LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2020

Sociedad Argentina de Investigación Clínica

Cancer Stem Cells (CSC) are the responsible of colorectal cancer (CRC) persistence. We have previously demonstrated that RAC3, a transcription coactivator usually overexpressed in CRC is required for maintaining CSC, with anti-apoptotic and anti-autophagy effect. Moreover, Aloysia polystachya (AP) extracts induce the cell death of CRC, in vivo and in vitro. Quercetin, an agonist of the AHR, was a flavonoid detected at high level as one of the AP components. In this work, we investigated the effects of quercetin and the probable AHR/CSC/RAC3 relationship in CSC of CRC. The effect of the flavonoid was investigated performing cytotoxicity assays in the human CRC HCT116wt cell line (overexpressing RAC3) or shRNA-RAC3 stimulated with different concentrations of quercetin for 24h. HEK293 cells (low levels of RAC3) were used as a non-tumoral control. The quercetin pathways and AHR/CSC/RAC3 relationship were investigated by bioinformatics studies using public repository microarrays data from the human CRC CaCo-2 cells, CD133+ or CD133− side populations, from rat CRC and from human CRC samples from TCGA, using Xena, consensusPathDB and STRING platforms. We found that quercetin induced a significant increased cytotoxicity of HCT116wt respect to shRNA-RAC3 HCT116 and HEK293 (p