Physiological and Molecular Role of Ranpirnase on Cancer Treatment

Intae      Lee; Daehong      Kim; Jihean      Lee; Kuslima      Shogen

doi:10.2174/157339410790596425

Abstract

Ranpirnase (ONCONASE®, a trademark of Alfacell Corporation), a cytotoxic amphibian ribonuclease, is known to be selectively tumoricidal against cancer cells. This article briefly summarizes in vitro and in vivo tumoricidal studies of ranpirnase. It proposes mechanisms of ranpirnase based on preclinical and clinical trials. Ranpirnase significantly inhibited oxygen consumption while demonstrating improvement in several tumor physiological parameters including tumor blood flow (TBF). Ranpirnase showed chemo-sensitization with various chemotherapeutic agents in vitro and in vivo. Ranpirnase significantly reduced the tumor hypertension, the major physiological barrier of therapeutic drug delivery to solid tumors. This resulted in increased tumor penetration and selectively increased TBF. This enhanced efficacy of chemotherapeutic agents including cisplatin and doxorubicin. The possible ranpirnase-related signal transduction pathways are discussed in the context of the enhanced induction of apoptosis and inhibition of protein synthesis. As a selective cancer killer ranpirnase may be a promising candidate for improving the treatment of mesothelioma and lung cancer patients.

Keywords: Ranpirnase, ONCONASE®, mesothelioma, lung cancer, apoptosis, protein inhibition, tumor hypertension, tumor blood flow