Ribonuclease as Anticancer Therapeutics

Abstract

Ribonucleases (RNases) are small molecules which are highly cytotoxic in nature. They catalyse the degradation of RNA into smaller molecules rapidly in an unprotected environment. The cytotoxic properties of RNases include degradation of RNA leading to blockage of protein synthesis in malignant cells and inducing the apoptosis response. Cytotoxicity of RNases is determined by catalytic activity, stability, non-selective nature of inhibitors, positive charge on molecule and internalization. Onconase, BS-RNase and other RNases exert cytotoxic activity on cancer cells selectively by involving different cellular pathways and/ or enhance the cytotoxicity by mutation. A general mechanism of the cytotoxic activity of RNases includes the interaction of the enzyme with the cellular membrane by non-specific interactions mediated by Coulombic forces, internalization by endocytosis, translocation to the cytosol, degradation of ribonucleic acid and subsequent cell death by activation of caspase-dependent mechanisms, low molecular weight compounds or alteration in protein and NF-κB signal pathway. But still it is unclear that which of these mechanisms is most potent, common and causes cell death in cancerous cells. The problem related to ribonuclease inhibitor (RI) has not fully elucidated. This article looks at the cellular pathways of RNases and mechanism of their cytotoxicity towards the malignant cells which makes RNase as a strong candidate to be considered as chemotherapeutic or antitumor drug. Some of the prominent approaches to exploit RNase molecule as an anticancer therapeutic agent have been discussed.

Bioactive compounds from fungi with antiviral activities: Mechanism of action and biosynthetic pathways

“…All microorganisms contain different classes of RNases, which are hydrolytic enzymes that are involved in degradation of phosphodiester bond of cellular RNA. In particular, Aspergillus is one of the most prominent fungal genera in terms of both production and medical applications of fungal RNases (Kumar & Kanwar, 2017;. However, RNases from Rhizopus niveus, Ustilago sphaerogena (Lacadena et al, 2007;Kumar & Kanwar, 2017, Fusarium moniliforme (Yoshida et al, 1980), Penicillium brevicompactum (Shlyapnikov et al, 1984) and Penicillium chrysogenum (Yakovlev et al, 1980) have also been studied.…”