The bacterial colicin active against tumor cells in vitro and in vivo is verotoxin 1.
We have identified verotoxin 1 (VT1) as the active component within an antineoplastic bacteriocin preparation from Escherichia coli HSC10 studied over two decades. Recombinant VT1 can simulate the toxicity of anticancer proteins (ACP), and the antineoplastic activity of ACP (and VT1) was abrogated by treatment with anti-VT1 antibody. Similarly, VT1 mimics the protective effect of ACP in a murine metastatic fibrosarcoma model. Prior immunization with VT1 B subunit prevents the effect of VT1 or ACP in this model. The activity of ACP against a variety of human ovarian cell lines was mimicked by VT1, and multidrug-resistant variants were significantly hypersensitive. Primary ovarian tumors and metastases contain elevated levels of globotriaosylceramide compared with normal ovaries, and overlay of frozen tumor sections showed selective VT binding to tumor tissue and the lumen of invading blood vessels. Our contention that VT1 could provide an additional approach to the management of certain human neoplasms is discussed.
Farkas-Himsley
H
H
Department of Microbiology, University of Toronto, ON Canada.
Hill
R
R
Rosen
B
B
Arab
S
S
Lingwood
C A
CA
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*; D003087:Colicins / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D003603:Cytotoxins / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000737:chemistry* / Q000276:immunology; D005260:Female; D006017:Glycolipids / Q000302:isolation & purification; D008175:Lung Neoplasms / Q000628:therapy; D051379:Mice; D010051:Ovarian Neoplasms / Q000473:pathology / Q000628:therapy; D011956:Receptors, Cell Surface / Q000302:isolation & purification; D022622:Shiga Toxin 1; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D001427:Bacterial Toxins; D003087:Colicins; D003603:Cytotoxins; D006017:Glycolipids; D011956:Receptors, Cell Surface; D022622:Shiga Toxin 1; C068556:Shiga-like toxin receptor