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PMID: 7624357 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The bacterial colicin active against tumor cells in vitro and in vivo is verotoxin 1.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 92 ·No. 15 ·1995-07-18 ·Pages 6996-7000

Farkas-Himsley H, Hill R, Rosen B, Arab S, Lingwood CA

Abstract

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.

MeSH Terms
Animals Antibiotics, Antineoplastic/chemistry,immunology,isolation & purification,pharmacology Bacterial Toxins/immunology,isolation & purification,pharmacology Colicins/chemistry,immunology,pharmacology Cytotoxins/immunology,isolation & purification,pharmacology Dose-Response Relationship, Drug Escherichia coli/chemistry,immunology Female Glycolipids/isolation & purification Lung Neoplasms/therapy Mice Ovarian Neoplasms/pathology,therapy Receptors, Cell Surface/isolation & purification Shiga Toxin 1 Tumor Cells, Cultured
Chemicals
Antibiotics, Antineoplastic Bacterial Toxins Colicins Cytotoxins Glycolipids Receptors, Cell Surface Shiga Toxin 1 Shiga-like toxin receptor
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Farkas-Himsley H
Department of Microbiology, University of Toronto, ON Canada.
Hill R
Rosen B
Arab S
Lingwood C A
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54 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.92.15.6996
Published
1995-07-18
Pages
6996-7000
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC41458
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.92.15.6996 PMC Full Text View journal details
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