EFFECT OF QUERCETIN ON THE LYSOSOME-DEPENDENT CELL DEATH PROCESS IN BREAST CANCER CELLS

PEREYRA L; PERALTA S; VARGAS-ROIG LM; SOSA MA; CARVELLI L

Mendoza

Congreso; XL Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2022

Sociedad de Biología de Cuyo

Breast cancer is the leading cause of death in women worldwide. Some tumor cells have shown an increased lysosomal biogenesis, together with an altered lysosomal integrity and/or functionality. Alterations in the lysosomal membrane permeability induce a release of proteases such as cathepsin D (CatD) into the cytoplasm, triggering apoptotic processes (lysosome-dependent cell death). Quercetin (Que) is a flavonoid highly used as an antioxidant, although it is known that in some types of tumors it has pro-oxidative effects. In breast cancer cells, Que induces cell death and upregulates lysosomal biogenesis, although its mechanism of action is still unclear. The aim of this study was to evaluate the effect of Que on the lysosome-dependent cell death process in MCF-7 human mammary tumor cells. Cell cultures incubated with Que (40 uM and 200 uM) for 8 and 24 h were processed for fluorescence microscopy and subcellular fractionation, followed by immunoblotting. In MCF-7 cells, Que treatments induced an apparent increase in the size of lysosomal compartments (labeled with LysoTrackerTM Red DND-99) compared to untreated control cells. In turn, the effect of Que on lysosomal membrane permeability was evaluated by studying the CatD leakage to the cytoplasm. Immunoblots revealed that Que did not produce significant changes on the presence of CatD in the cytoplasmic fraction. Our results would indicate that Que does not trigger apoptosis through lysosomal membrane rupture in breast cancer cells, although other mechanisms involving lysosomes should not be ruled out.