Artículo
AhR ligand Aminoflavone inhibits α6-integrin expression and breast cancer sphere-initiating capacity
Brantley, Eileen; Callero, Mariana Alejandra
; Berardi, Damian Emilio
; Campbell, Petreena; Rowland, Leah; Zylstra, Dain; Amis, Louisa; Yee, Michael; Simian, Marina
; Todaro, Laura Beatriz
; Loaiza Perez, Andrea Irene
; Soto, Ubaldo
Fecha de publicación:
06/2016
Editorial:
Elsevier Ireland
Revista:
Cancer Letters
ISSN:
0304-3835
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Traditional chemotherapies debulk tumors but fail to produce long-term clinical remissions due to their inability to eradicate tumor-initiating cells (TICs). This necessitates therapy with activity against the TIC niche. Alpha6-integrin (α6-integrin) promotes TIC growth. In contrast, aryl hydrocarbon receptor (AhR) signaling activation impedes the formation of mammospheres (clusters of cells enriched for TICs). We investigated the ability of AhR agonist Aminoflavone (AF) and AF pro-drug (AFP464) to disrupt mammospheres derived from breast cancer cells and a M05 mammary mouse model of breast cancer respectively. We further examined the capacity of AF and AFP464 to exhibit anticancer activity and modulate the expression of 'stemness' genes including α6-integrin using immunofluorescence, flow cytometry and qRT-PCR analysis. AF disrupted mammospheres and prevented secondary mammosphere formation. In contrast, AF did not disrupt mammospheres derived from AhR ligand-unresponsive MCF-7 cells. AFP464 treatment suppressed M05 tumor growth and disrupted corresponding mammospheres. AF and AFP464 reduced the expression and percentage of cells that stained for 'stemness' markers including α6-integrin in vitro and in vivo respectively. These data suggest AFP464 thwarts bulk breast tumor and TIC growth via AhR agonist-mediated α6-integrin inhibition.
Palabras clave:
Aminoflavone
,
Aryl Hydrocarbon Receptor
,
Mammospheres
,
Α6-Integrin
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Articulos(OCA HOUSSAY)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Citación
Brantley, Eileen; Callero, Mariana Alejandra; Berardi, Damian Emilio; Campbell, Petreena; Rowland, Leah; et al.; AhR ligand Aminoflavone inhibits α6-integrin expression and breast cancer sphere-initiating capacity; Elsevier Ireland; Cancer Letters; 376; 1; 6-2016; 53-61
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