IHEM   20887
INSTITUTO DE HISTOLOGIA Y EMBRIOLOGIA DE MENDOZA DR. MARIO H. BURGOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Effect of tamoxifen and ammonium chloride on acidic compartments in human breast cancer cells
Autor/es:
PEREYRA L; VARGAS-ROIG LM; CHAPANA A; CARVELLI L; BANNOUD N; SOSA MA
Lugar:
Mendoza
Reunión:
Simposio; II Simposio Internacional de Medicina Traslacional; 2019
Institución organizadora:
Facultad de Ciencias Médicas, Universidad Nacional de Cuyo
Resumen:
Introduction. Breast cancer is a heterogeneous disease that accounts a third of all cancers diagnosed in women and over half a million deaths per year. In estrogen receptor (ER)-positive breast cancer, a treatment with the anti-estrogenic drug Tamoxifen (TAM) reduces mortality due a modulation hormone-dependent in those tumors. However, it is possible that TAM could exert effects by mechanisms other than interaction with ERs. In fact, TAM has an affinity for lysosomes. Objective. To evaluate the lysosome status in breast cell lines throughout the counting of acidic compartments, after treatment with TAM or the lysosomotropic drug NH4Cl. Methodology. Lysotracker was used as a marker of acidic compartments. Tumor cells lines, MCF-7 (ER-positive) and MDA-MB-231 (ER-negative), were incubated at different times with NH4Cl or TAM, either in the presence or the absence of 17-β-estradiol. The number of acidic compartment (AC) was evaluated by fluorescence microscopy. The non-tumorigenic cell line MCF-10A was used as a control. Results. After treatment with NH4Cl, we observed: a) in all cell lines, a decreased level of AC after 2 h of exposure, b) in tumoral cells, the number of AC was recovered at 8 h of incubation, whereas non-tumorigenic cells, it was at 24h. After treatment with TAM, we observed: a) in tumorigenic cell lines, AC levels tend to decrease after 8 h, and normal cells did it after 24 h, b) in the MDA-MB-231 cells, basal levels of AC were recovered at 24 h.Conclusion. a) in breast cancer cells, TAM could act as a lysosomotropic drug, although at a lesser extent than NH4Cl, b) NH4Cl could leave the AC at longer incubation, being faster in the tumoral cells, and c) TAM could also leave the AC in the MDA-MB-231 cells possibly by a different mechanism than NH4Cl.