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Selective cytotoxicity of recombinant STXA1-GM-CSF protein in hematopoetic cancer cells

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Abstract

Chimeric proteins are composed of a cell-targeting moiety and a cell-killing moiety. In this study, a chimeric protein, STXA1-GM-CSF, composed of catalytic domain of Shiga toxin (A1) and granulocyte-macrophage colony-stimulating factor (GM-CSF) was constructed and expressed in E. coli. Cytotoxicity, receptor blocking, and neutralization experiments revealed that the chimeric protein induced cytotoxic effect on different cell lines. This effect was found to be specific, due to the presence of the killing moiety (A1), which exerts its effect through a specific GM-CSF-targeting domain, by binding to its receptor present on those cell lines. These initial investigations indicate that the chimeric protein was functional; further analyses are required for its application.

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Abbreviations

AML:

acute myeloid leukemia

(h)GM-CSF:

(human) granulocyte-macrophage colony-stimulating factor

MTT:

3-3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyletrazolium bromide

RIP:

ribosome-inactivating protein

SDS-PAGE:

sodium docecyl sulfate–polyacrylamide gel electrophoresis

SLT:

Shiga-like toxin

STX:

Shiga toxin

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Correspondence to S. Bouzari.

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Roudkenar, M.H., Jafari, A., Oloomi, M. et al. Selective cytotoxicity of recombinant STXA1-GM-CSF protein in hematopoetic cancer cells. Cell Biol Toxicol 22, 213–219 (2006). https://doi.org/10.1007/s10565-006-0051-y

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  • DOI: https://doi.org/10.1007/s10565-006-0051-y

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