Ribonucleases as novel chemotherapeutics : the ranpirnase example.
Ranpirnase, a cytotoxic ribonuclease from the frog Rana pipiens, is the archetype of a novel class of cancer chemotherapeutic agents based on homologs and variants of bovine pancreatic ribonuclease (RNase A). Ranpirnase in combination with doxorubicin is in clinical trials for the treatment of unresectable malignant mesothelioma and other cancers. The putative mechanism for ranpirnase-mediated cytotoxicity involves binding to anionic components of the extracellular membrane, cytosolic internalization, and degradation of transfer RNA leading to apoptosis. The maintenance of ribonucleolytic activity in the presence of the cytosolic ribonuclease inhibitor protein is a key aspect of the cytotoxic activity of ranpirnase. The basis for its specific toxicity for cancer cells is not known. This review describes the development of ranpirnase as a cancer chemotherapeutic agent.
Lee
J Eugene
JE
Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706-1544, USA.
Raines
Ronald T
RT
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D015202:Protein Engineering; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011894:Rana pipiens; D012260:Ribonucleases / Q000494:pharmacology* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D011500:Protein Synthesis Inhibitors; D012260:Ribonucleases; C058703:ranpirnase