Title : Arsenate target specific cell death mechanism in normal and tumoral breast cancer cell lines
Arsenate was demonstrated to be implicated in a wide range of cellular and molecular pathways. These multiple actions of arsenate highlight the need for additional mechanistic studies to determine which actions mediate the diverse biological effects of this compound as an environmental toxic agent or therapeutic target. Our study was focused on the evaluation the response to a low dose (50nM) of arsenate in a panel of normal (HMEC) and tumoral breast cancer (MCF7, Hs578T and MDA-MB-231). Microscopy results showed that arsenate induced cytoskeletal alteration, as well as increased autophagy and apoptosis rate in the breast cancer cell lines, none of which was seen in the normal breast cell line. Arsenate treatment specifically induces autophagy, apoptosis and cytoskeletal alteration, these effects being more pronounced on tumor cells than in the normal breast cancer cell line. Additional gene expression microarray evaluation (Agilent technology) was done, showing that arsenate induced important alteration on the transcriptomic patterns, these being cell type-specific. These alterations were related to autophagy, apoptosis, epigenetic alteration and DNA damage signaling. Furthermore, we revealed an activation of a panel of genes responsible for promoting drug resistance. Our study provides new insights on mechanistic understanding of the toxicity of arsenate and might have an important role in the development of more effective therapeutic interventions.