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Aspects of the Cytotoxic Action of Ribonucleases

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By virtue of their RNA degrading catalytic activity, ribonucleases are potentially cytotoxic. For the application of these enzymes as therapeutics, however, they have to overcome several obstacles whose interplay is not yet fully understood. Ribonucleases with a basic pI are not only able to interact with the (negatively charged) cellular membrane but they are also distinctively selective for tumor cells. After the (endocytotic) uptake into the cell and release into the cytosol from the endosomes where they have to resist the attack by proteases, they face the cytosolic ribonuclease inhibitor. Only if they are able to evade the tight binding to the inhibitor (or if enough ribonuclease molecules enter the cell to neutralize the inhibitor protein) they are able to attack their target RNA, for which a sufficient ribonucleolytic activity is indispensable. Each of these steps can turn into an insurmountable hurdle spoiling the cytotoxic potential of these enzymes.

In the present review I will summarize the status quo of the knowledge on the mechanisms and their interdependence as well as to develop strategies to overcome possible limitations.

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Keywords: Ribonuclease; antitumor; cytotoxicity; internalization; stability; therapeutic

Document Type: Research Article

Publication date: 01 June 2008

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  • Current Pharmaceutical Biotechnology aims to cover all the latest and outstanding developments in Pharmaceutical Biotechnology. Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics in both pre-clinical and clinical areas of Pharmaceutical Biotechnology. Current Pharmaceutical Biotechnology is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments.
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