DUGi

Onconase, a ribonuclease with antitumor and antiviral properties

http://dugi.udg.edu/item/http:@@@@hdl.handle.net@@10256@@20533

This research work is about the enzyme onconase. It’s a ribonuclease (RNase) that belongs to the superfamily of pancreatic ribonucleases and that at present is used in clinical trials as antitumoral and antiviral agent. The main objective of this work is to describe the molecular mechanisms that are responsible for the antiviral and antitumor activities of onconasa. First, its molecular structure is described because it is different from that presented by other ribonucleases of the same family. This 3D-structure endows onconasa with a high stability. It is described the molecular mechanism that likely explain its selective cytotoxicity for tumor cells and for cells infected by different virus. In addition, it is discussed the hypothesis that explain its translocation to the cytosol, the process of RNA degradation and the induction of apoptosis of tumor cells. It is important to remark that onconase does not produce apoptosis only by arresting protein synthesis due to a degradation of different RNAs. It is described that onconase also induces the overexpression of certain RNAs, suggesting that other mechanism are involved in the apoptosis induced by this enzyme. As antiviral agent, it is described the mechanism that onconase uses to degrade viral RNA or the necessary elements for viral replication. Moreover, it is discussed some particular cases of specific viruses that are efficiently affected by onconase. As antitumor agent, it is analyzed the capacity of onconase to amplify the action of certain compounds that are used as chemotherapeutics agents to fight certain types of cancers, i.e., its synergy with these antitumor agents. Although the mechanism of this enzyme is not completely known, it has been observed to be highly effective against the action of some viruses (such as human immunodeficiency virus, human papilloma virus or rabies virus) and tumor cells. Because onconase is a ribonuclease, it doesn’t act on DNA and does not cause mutations (drugs that act on DNA can be mutagenic and produce the appearance of cancers) i.e., it is not genotoxic. For all these reasons, onconase can become a highly effective drug