Artículo
Histamine prevents radiation-induced mesenchymal changes in breast cancer cells
Galarza, Tamara Ester
; Mohamad, Nora Alicia; Táquez Delgado, Mónica Alejandra
; Vedoya, Guadalupe M.; Crescenti, Ernesto J.; Bergoc, Rosa Maria
; Martin, Gabriela Adriana
; Cricco, Graciela Patricia
Fecha de publicación:
09/2016
Editorial:
Academic Press Ltd - Elsevier Science Ltd
Revista:
Pharmacological Research
ISSN:
1043-6618
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Radiotherapy is a prime option for treatment of solid tumors including breast cancer though side effects are usually present. Experimental evidence shows an increase in invasiveness of several neoplastic cell types through conventional tumor irradiation. The induction of epithelial to mesenchymal transition is proposed as an underlying cause of metastasis triggered by gamma irradiation. Experiments were conducted to investigate the role of histamine on the ionizing radiation-induced epithelial to mesenchymal transition events in breast cancer cells with different invasive phenotype. We also evaluated the potential involvement of Src phosphorylation in the migratory capability of irradiated cells upon histamine treatment. MCF-7 and MDA-MB-231 mammary tumor cells were exposed to a single dose of 2 Gy of gamma radiation and five days after irradiation mesenchymal-like phenotypic changes were observed by optical microscope. The expression and subcellular localization of E-cadherin, β-catenin, vimentin and Slug were determined by immunoblot and indirect immunofluorescence. There was a decrease in the epithelial marker E-cadherin expression and an increase in the mesenchymal marker vimentin after irradiation. E-cadherin and β-catenin were mainly localized in cytoplasm. Slug positive nuclei, matrix metalloproteinase-2 activity and cell migration and invasion were significantly increased. In addition, a significant enhancement in Src phosphorylation/activation could be determined by immunoblot in irradiated cells. MCF-7 and MDA-MB-231 cells also received 1 or 20 μM histamine during 24 h previous to be irradiated. Notably, pre-treatment of breast cancer cells with 20 μM histamine prevented the mesenchymal changes induced by ionizing radiation and also reduced the migratory behavior of irradiated cells decreasing phospho-Src levels. Collectively, our results suggest that histamine may block events related to epithelial to mesenchymal transition in irradiated mammary cancer cells and open a perspective for the potential use of histamine to improve radiotherapy efficacy.
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Articulos(OCA HOUSSAY)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Citación
Galarza, Tamara Ester; Mohamad, Nora Alicia; Táquez Delgado, Mónica Alejandra; Vedoya, Guadalupe M.; Crescenti, Ernesto J.; et al.; Histamine prevents radiation-induced mesenchymal changes in breast cancer cells; Academic Press Ltd - Elsevier Science Ltd; Pharmacological Research; 111; 9-2016; 731-739
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