Targeting Cell Death Mechanism Specifically in Triple Negative Breast Cancer Cell Lines.


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Authors
Pruteanu, Lavinia-Lorena 
Jurj, Maria-Ancuţa 
Raduly, Lajos-Zsolt  ORCID logo  https://orcid.org/0000-0002-3926-5423
Abstract

Triple negative breast cancer (TNBC) is currently associated with a lack of treatment options. Arsenic derivatives have shown antitumoral activity both in vitro and in vivo; however, their mode of action is not completely understood. In this work we evaluate the response to arsenate of the double positive MCF-7 breast cancer cell line as well as of two different TNBC cell lines, Hs578T and MDA-MB-231. Multimodal experiments were conducted to this end, using functional assays and microarrays. Arsenate was found to induce cytoskeletal alteration, autophagy and apoptosis in TNBC cells, and moderate effects in MCF-7 cells. Gene expression analysis showed that the TNBC cell lines' response to arsenate was more prominent in the G2M checkpoint, autophagy and apoptosis compared to the Human Mammary Epithelial Cells (HMEC) and MCF-7 cell lines. We confirmed the downregulation of anti-apoptotic genes (MCL1, BCL2, TGFβ1 and CCND1) by qRT-PCR, and on the protein level, for TGFβ2, by ELISA. Insight into the mode of action of arsenate in TNBC cell lines it is provided, and we concluded that TNBC and non-TNBC cell lines reacted differently to arsenate treatment in this particular experimental setup. We suggest the future research of arsenate as a treatment strategy against TNBC.

Description
Keywords
triple negative breast cancer, breast cancer, gene expression, arsenate, microarray, mode of action
Journal Title
Int J Mol Sci
Conference Name
Journal ISSN
1661-6596
1422-0067
Volume Title
23
Publisher
MDPI
Sponsorship
Unitatea Executiva Pentru Finantarea Invatamantului Superior a Cercetarii Dezvoltarii si Inovarii (PN-III-P1-1.2-PCCDI-2017-0737, CANCERTER-p53)