SHIGA TOXIN FROM ENTEROHEMORRHAGIC E. COLI AS A NOVEL AGENT AGAINST TRIPLE NEGATIVE BREAST CANCER

PINTO A.; MIRET N.; RANDI A. ; GOLDSTEIN J

Congreso; Reunion Anual de Sociedades de Biociencias; 2023

Shiga toxin (Stx) is responsible for producing the hemolytic-uremic syndrome. There are two types of Stxs, Stx1 and Stx2 which are about 60% homologous. Classically, the Stx cytotoxic effect is mediated by its receptor globotriaosylceramide (Gb3). Gb3 has a restricted profile of tissue expression in normal human cells and it is overexpressed in many neoplastic cells, including breast tumors. Breast cancer is the most common malignancy and the leading cause of cancer-related death in women worldwide. Triple negative breast cancer (TNBC) is the most aggressive and difficult to treat from all breast tumors. Thus, the aim of this study was to determine the potential of Stx as a novel cytotoxic agent in the TNBC human cell line MDA-MB-231. For this purpose, cells were treated with Stx1, Stx2 or the antibody anti-Gb3. Moreover, the non-tumorigenic mammary epithelial cell line NMuMG and VERO cells (highly sensitive to Stx kidney epithelial cells extracted from the African green monkey) were used as a negative and a positive control of Gb3 expression. Gb3 content and Stx uptake were observed by immunofluorescence in MDA-MB-231 and VERO cells. MTT results showed that 10 ng/ml of Stx1 and Stx2 reduced respectively 50% and 40% the cell viability after 48h (p