The Nuclease from Gram-Negative Bacteria Serratia Marcescens is Weakly Cytotoxic at Therapeutic Doses

Abstract

The nuclease from S.marcescens heads a family of homological nonspecific nucleases. Its cultivation features, structure, mechanism of action, some physical, chemical and biochemical properties are well studied. It is presented by two isoforms, differing by N-terminal fragment and some properties. The nuclease demonstrated a cancer suppressing effect in mice. It is a key component of the anti-rabies composition which increases survival of the infected mice. It is similar by its efficiency to Pulmozyme® that is used for airway cleansing during the treatment of pulmonary diseases. The aim of the study was to analyze a cytotoxic effect of S. marcescens nuclease and its separate isoforms at different concentrations. To determine the cytotoxicity we used MTT assay and human cell cultures of colorectal cancer -HCT 116, breast cancer MCF-7 and normal skin fibroblasts. Results show that the nuclease demonstrates a weak cytotoxic effect at the amounts of 0.2 – 25 µg per 1 ml of the cell culture medium that is close to its therapeutic doses. This effect is not connected with the loss of the enzymatic activity. The isoforms are similar by their IC50.