PARADOXICAL ANTINEOPLASTIC EFFECT OF SHIGA TOXIN 2 FROM ENTEROHEMORRHAGIC ESCHERICHIA COLI IN TRIPLE-NEGATIVE BREAST CANCER CELLS

ALIPIO PINTO; NOELIA MIRET; LORENA ZÁRATE; ANDREA RANDI; JORGE GOLDSTEIN

Virtual

Congreso; Reunión Anual de Sociedades de Biociencias; 2020

Sociedad Argentina de Investigación Clínica, Sociedad Argentina de Fisiología y Sociedad Argentina de Inmunología

Shiga toxin 2 (Stx2) is avirulence factor responsiblefor hemolytic uremic syndrome. Classically, theStx2´s cytotoxic effect is mediated by its receptor globotriaosylceramide(Gb3). Furthermore, it has been observed that malignant cells represent a greatsource of Gb3. One of theseGb3-producing malignant tumors is breast cancer,which is the most common cancer type in women worldwide. Triple-negative breastcancer (TNBC) is the most aggressive and difficult to treat from all breasttumors. Our goal is to determine the antineoplastic effect of Stx2 in the TNBCcell line MDA-MB-231.The non-tumorigenic mammary epithelial cell line NMuMG,which lacks Gb3(negative control), and VERO cells (positive control) were used.Gb3 expression was immunolocalized in MDA-MB-231 and VERO cells, and Stx2uptake was alsoobserved in both cell lines, with higher levels in VERO cells(p<0.0001). Besides, Gb3 levels were increased after Stx2 treatment inMDA-MB-231 cells (p<0.007). MTT results showed that 1 and 10 ng/ml Stx2reduced cell viability after 12, 18, 24 and 48h (p<0.05). A Stx2dose-dependent cytotoxic effect was found in MDA-MB-231 cells after 48h(p<0.05). This action was accompanied by an increase of karyorrhexis(p<0.0001) and a reduction of mitosis only in MDA-MB-231 and in VERO cells(p<0.0004), analyzed by immunofluorescence. With the purpose of evaluatingwhether an anti-Gb3 antibody would be able to trigger a cellular response, 10ng/ml of anti-Gb3 or combined with Stx2 was assayed. A cytotoxic effect ofanti-Gb3 was observed by MTT in MDA-MB-231, but with less potency than thatproduced by Stx2 itself (p<0.05) and no synergism was found between them.These results suggest that MDA-MB-231cells are susceptible-dose dependent toStx2 and sensitive to anti-Gb3 antibodies. Further studies are necessary toevaluate the safety andeffectiveness of Stx2 or anti-Gb3 as a potentialtreatment in TNBC.<!-- /* Font Definitions */ @font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:roman;mso-font-pitch:variable;mso-font-signature:-536870145 1107305727 0 0 415 0;}@font-face{font-family:Calibri;panose-1:2 15 5 2 2 2 4 3 2 4;mso-font-charset:0;mso-generic-font-family:swiss;mso-font-pitch:variable;mso-font-signature:-536859905 -1073732485 9 0 511 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin:0cm;mso-pagination:widow-orphan;font-size:12.0pt;font-family:"Calibri",sans-serif;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:ES-TRAD;mso-fareast-language:EN-US;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-family:"Calibri",sans-serif;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-fareast-language:EN-US;}size:612.0pt 792.0pt;margin:70.85pt 3.0cm 70.85pt 3.0cm;mso-header-margin:36.0pt;mso-footer-margin:36.0pt;mso-paper-source:0;}div.WordSection1{page:WordSection1;}