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Cytotoxicity of RNase Sa to the acute myeloid leukemia Kasumi-1 cells depends on the net charge
The majority of known cytotoxic RNases are basic proteins which destroy intracellular RNA. Cationization of RNases is considered to be an effective strategy for strengthening their antitumor properties. We constructed a set of RNase Sa variants consisting of charge reversal mutants, charge neutraliz...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278273/ https://www.ncbi.nlm.nih.gov/pubmed/25594000 |
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author | Mitkevich, Vladimir A. Burnysheva, Ksenia M. Ilinskaya, Olga N. Pace, C. Nick Makarov, Alexander A. |
author_facet | Mitkevich, Vladimir A. Burnysheva, Ksenia M. Ilinskaya, Olga N. Pace, C. Nick Makarov, Alexander A. |
author_sort | Mitkevich, Vladimir A. |
collection | PubMed |
description | The majority of known cytotoxic RNases are basic proteins which destroy intracellular RNA. Cationization of RNases is considered to be an effective strategy for strengthening their antitumor properties. We constructed a set of RNase Sa variants consisting of charge reversal mutants, charge neutralization mutants, and variants with positively charged cluster at the N-terminus. All constructs retain a high level of catalytic activity and differ in net charge. Using acute myeloid leukemia cells Kasumi-1 we have shown that (i) cytotoxicity of RNase Sa mutants is linearly enhanced by cationization, (ii) the ability of cytotoxic mutants to induce cell death is caused by induction of apoptosis and (iii) localization of positive charge on N-terminus does not contribute to RNase Sa cytotoxicity. Capacity to induce apoptosis in malignant cells and the absence of necrotic effects make the RNase Sa mutants with high positive charge a suitable anti-cancer agent. |
format | Online Article Text |
id | pubmed-4278273 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-42782732015-01-15 Cytotoxicity of RNase Sa to the acute myeloid leukemia Kasumi-1 cells depends on the net charge Mitkevich, Vladimir A. Burnysheva, Ksenia M. Ilinskaya, Olga N. Pace, C. Nick Makarov, Alexander A. Oncoscience Research Paper The majority of known cytotoxic RNases are basic proteins which destroy intracellular RNA. Cationization of RNases is considered to be an effective strategy for strengthening their antitumor properties. We constructed a set of RNase Sa variants consisting of charge reversal mutants, charge neutralization mutants, and variants with positively charged cluster at the N-terminus. All constructs retain a high level of catalytic activity and differ in net charge. Using acute myeloid leukemia cells Kasumi-1 we have shown that (i) cytotoxicity of RNase Sa mutants is linearly enhanced by cationization, (ii) the ability of cytotoxic mutants to induce cell death is caused by induction of apoptosis and (iii) localization of positive charge on N-terminus does not contribute to RNase Sa cytotoxicity. Capacity to induce apoptosis in malignant cells and the absence of necrotic effects make the RNase Sa mutants with high positive charge a suitable anti-cancer agent. Impact Journals LLC 2014-11-10 /pmc/articles/PMC4278273/ /pubmed/25594000 Text en © 2014 Mitkevich et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Mitkevich, Vladimir A. Burnysheva, Ksenia M. Ilinskaya, Olga N. Pace, C. Nick Makarov, Alexander A. Cytotoxicity of RNase Sa to the acute myeloid leukemia Kasumi-1 cells depends on the net charge |
title | Cytotoxicity of RNase Sa to the acute myeloid leukemia Kasumi-1 cells depends on the net charge |
title_full | Cytotoxicity of RNase Sa to the acute myeloid leukemia Kasumi-1 cells depends on the net charge |
title_fullStr | Cytotoxicity of RNase Sa to the acute myeloid leukemia Kasumi-1 cells depends on the net charge |
title_full_unstemmed | Cytotoxicity of RNase Sa to the acute myeloid leukemia Kasumi-1 cells depends on the net charge |
title_short | Cytotoxicity of RNase Sa to the acute myeloid leukemia Kasumi-1 cells depends on the net charge |
title_sort | cytotoxicity of rnase sa to the acute myeloid leukemia kasumi-1 cells depends on the net charge |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278273/ https://www.ncbi.nlm.nih.gov/pubmed/25594000 |
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