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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...

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Detalles Bibliográficos
Autores principales: Mitkevich, Vladimir A., Burnysheva, Ksenia M., Ilinskaya, Olga N., Pace, C. Nick, Makarov, Alexander A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2014
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.
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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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