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Research Paper
The Interdependence Between Catalytic Activity, Conformational Stability and Cytotoxicity of Onconase
Cindy Schulenburg, Barbara Ardelt, Wojciech Ardelt, Ulrich Arnold, Kuslima Shogen, Renate Ulbrich-Hofmann and Zbigniew Darzynkiewicz
volume 6 | issue 8
August 2007Pages: 1233 - 1239
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Onconase (ONC) is a cytotoxic ribonuclease of the pancreatic RNase A superfamily isolated from oocytes or early embryos of the Northern leopard frog (Rana pipiens). It shows anticancer activity and currently is in Phase IIIb clinical trial for unresectable malignant mesothelioma. We generated several variants of ONC possessing mutations in selected structural regions of the molecule that have altered ribonucleolytic activity and/or conformational stability. The relationship between the stability and ribonucleolytic activity of these variants and their cytostatic and cytotoxic properties was investigated on several tumor cell lines. Similar as ONC, all variants were inducing reproductive cell death detected by reduced clonogenicity. The surviving cells proliferated at reduced rates as reflected by diminished size of colonies and prolongation of G0/1 phase of the cell cycle. Some cells were undergoing apoptosis. The cytotoxic and cytostatic effects of ONC and its variants were predominantly determined by their catalytic activity rather than by conformational stability.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.