Oncotarget

Research Papers:

Human recombinant truncated RNASET2, devoid of RNase activity; A potential cancer therapeutic agent

Liron Nesiel-Nuttman _, Betty Schwartz and Oded Shoseyov

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Oncotarget. 2014; 5:11464-11478. https://doi.org/10.18632/oncotarget.2562

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Abstract

Liron Nesiel-Nuttman1, Betty Schwartz2, Oded Shoseyov1

1The Robert H. Smith Institute of Plant Science and Genetics in Agriculture, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, 76100, ISRAEL

2School of Nutritional Sciences Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, 76100, ISRAEL

Correspondence to:

Betty Schwartz, e-mail: betty.schwartz@mail.huji.ac.il

Oded Shoseyov, e-mail: oded.shoseyov@collplant.com

Keywords: actin-binding, antitumorigenesis, antiangiogenesis, ribonuclease, trT2-50

Received: September 18, 2014     Accepted: October 01, 2014     Published: November 11, 2014

ABSTRACT

Human RNASET2 has been implicated in antitumorigenic and antiangiogenic activities, independent of its ribonuclease capacities. We constructed a truncated version of human RNASET2, starting at E50 (trT2-50) and devoid of ribonuclease activity. trT2-50 maintained its ability to bind actin and to inhibit angiogenesis and tumorigenesis. trT2-50 binds to cell surface actin and formed a complex with actin in vitro. The antiangiogenic effect of this protein was demonstrated in human umbilical vein endothelial cells (HUVECs) by its ability to arrest tube formation on Matrigel, induced by angiogenic factors. Immunofluorescence staining of HUVECs showed nuclear and cytosolic RNASET2 protein that was no longer detectable inside the cell following trT2-50 treatment. This effect was associated with disruption of the intracellular actin network. trT2-50 co-localized with angiogenin, suggesting that both molecules bind (or compete) for similar cellular epitopes. Moreover, trT2-50 led to a significant inhibition of tumor development. Histological analysis demonstrated abundant necrotic tissue and a substantial loss of endothelial structure in trT2-50-treated tumors. Collectively, the present results indicate that trT2-50, a molecule engineered to be deficient of its catalytic activity, still maintained its actin binding and anticancer-related biological activities. We therefore suggest that trT2-50 may serve as a potential cancer therapeutic agent.


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