Supramolecular organization as a factor of ribonuclease cytotoxicity

One of the approaches used to eliminate tumor cells is directed destruction/modification of their RNA molecules. In this regard, ribonucleases (RNases) possess a therapeutic potential that remains largely unexplored. It is believed that the biological effects of secreted RNases, namely their antitumor and antiviral properties, derive from their catalytic activity. However, a number of recent studies have challenged the notion that the activity of RNases in the manifestation of selective cytotoxicity towards cancer cells is exclusively an enzymatic one. In this review, we have analyzed available data on the cytotoxic effects of secreted RNases, which are not associated with their catalytic activity, and we have provided evidence that the most important factor in the selective apoptosis-inducing action of RNases is the structural organization of these enzymes, which determines how they interact with cell components. The new idea on the preponderant role of non-catalytic interactions between RNases and cancer cells in the manifestation of selective cytotoxicity will contribute to the development of antitumor RNase-based drugs.