title: Shiga toxin 1, as DNA repair inhibitor, synergistically potentiates the activity of the anticancer drug, mafosfamide, on raji cells.
abstract: Shiga toxin 1 (Stx1), produced by pathogenic Escherichia coli, targets a restricted subset of human cells, which possess the receptor globotriaosylceramide (Gb3Cer/CD77), causing hemolytic uremic syndrome. In spite of the high toxicity, Stx1 has been proposed in the treatment of Gb3Cer/CD77-expressing lymphoma. Here, we demonstrate in a Burkitt lymphoma cell model expressing this receptor, namely Raji cells, that Stx1, at quasi-non-toxic concentrations (0.05-0.1 pM), inhibits the repair of mafosfamide-induced DNA alkylating lesions, synergistically potentiating the cytotoxic activity of the anticancer drug. Conversely, human promyelocytic leukemia cells HL-60, which do not express Gb3Cer/CD77, were spared by the toxin as previously demonstrated for CD34+ human progenitor cells, and hence, in this cancer model, no additive nor synergistic effects were observed with the combined Stx1/mafosfamide treatment. Our findings suggest that Stx1 could be used to improve the mafosfamide-mediated purging of Gb3Cer/CD77+ tumor cells before autologous bone marrow transplantation.
authors: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Via San Giacomo 14, Bologna, Italy. maurizio.brigotti@unibo.it
authors: Maurizio
authors: M
authors: Brigotti
authors: Valentina
authors: V
authors: Arfilli
authors: Domenica
authors: D
authors: Carnicelli
authors: Laura
authors: L
authors: Rocchi
authors: Cinzia
authors: C
authors: Calcabrini
authors: Francesca
authors: F
authors: Ricci
authors: Pasqualepaolo
authors: P
authors: Pagliaro
authors: Pier Luigi
authors: PL
authors: Tazzari
authors: Roberta R
authors: RR
authors: Alfieri
authors: Pier Giorgio
authors: PG
authors: Petronini
authors: Piero
authors: P
authors: Sestili
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004260:DNA Repair / Q000187:drug effects; D004357:Drug Synergism; D018922:HL-60 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D011500:Protein Synthesis Inhibitors / Q000008:administration & dosage*; D022622:Shiga Toxin 1 / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D011500:Protein Synthesis Inhibitors; D022622:Shiga Toxin 1; C048341:mafosfamide; D003520:Cyclophosphamide