Ribonucleases as novel chemotherapeutics - The ranpirnase example

被引：84

作者：

Lee, J. Eugene ^{[1
,2
]}

Raines, Ronald T. ^{[1
,3
]}

机构：

[1] Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA

[2] CALTECH, Div Biol, Pasadena, CA 91125 USA

[3] Univ Wisconsin, Dept Chem, Madison, WI 53706 USA

来源：

BIODRUGS | 2008年 / 22卷 / 01期

关键词：

D O I：

10.2165/00063030-200822010-00006

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：53 / 58

页数：6

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