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Anthracyclines Suppress Both NADPH Oxidase- Dependent and -Independent NETosis in Human Neutrophils

Neutrophil extracellular traps (NETs) are cytotoxic DNA-protein complexes that play positive and negative roles in combating infection, inflammation, organ damage, autoimmunity, sepsis and cancer. However, NETosis regulatory effects of most of the clinically used drugs are not clearly established. S...

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Autores principales: Khan, Meraj A., D’Ovidio, Adam, Tran, Harvard, Palaniyar, Nades
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770146/
https://www.ncbi.nlm.nih.gov/pubmed/31500300
http://dx.doi.org/10.3390/cancers11091328
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author Khan, Meraj A.
D’Ovidio, Adam
Tran, Harvard
Palaniyar, Nades
author_facet Khan, Meraj A.
D’Ovidio, Adam
Tran, Harvard
Palaniyar, Nades
author_sort Khan, Meraj A.
collection PubMed
description Neutrophil extracellular traps (NETs) are cytotoxic DNA-protein complexes that play positive and negative roles in combating infection, inflammation, organ damage, autoimmunity, sepsis and cancer. However, NETosis regulatory effects of most of the clinically used drugs are not clearly established. Several recent studies highlight the relevance of NETs in promoting both cancer cell death and metastasis. Here, we screened the NETosis regulatory ability of 126 compounds belonging to 39 classes of drugs commonly used for treating cancer, blood cell disorders and other diseases. Our studies show that anthracyclines (e.g., epirubicin, daunorubicin, doxorubicin, and idarubicin) consistently suppress both NADPH oxidase-dependent and -independent types of NETosis in human neutrophils, ex vivo. The intercalating property of anthracycline may be enough to alter the transcription initiation and lead NETosis inhibition. Notably, the inhibitory doses of anthracyclines neither suppress the production of reactive oxygen species that are necessary for antimicrobial functions nor induce apoptotic cell death in neutrophils. Therefore, anthracyclines are a major class of drug that suppresses NETosis. The dexrazoxane, a cardioprotective agent, used for limiting the side effects of anthracyclines, neither affect NETosis nor alter the ability of anthracyclines to suppress NETosis. Hence, at correct doses, anthracyclines together with dexrazoxane could be considered as a therapeutic candidate drug for suppressing unwanted NETosis in NET-related diseases.
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spelling pubmed-67701462019-10-30 Anthracyclines Suppress Both NADPH Oxidase- Dependent and -Independent NETosis in Human Neutrophils Khan, Meraj A. D’Ovidio, Adam Tran, Harvard Palaniyar, Nades Cancers (Basel) Article Neutrophil extracellular traps (NETs) are cytotoxic DNA-protein complexes that play positive and negative roles in combating infection, inflammation, organ damage, autoimmunity, sepsis and cancer. However, NETosis regulatory effects of most of the clinically used drugs are not clearly established. Several recent studies highlight the relevance of NETs in promoting both cancer cell death and metastasis. Here, we screened the NETosis regulatory ability of 126 compounds belonging to 39 classes of drugs commonly used for treating cancer, blood cell disorders and other diseases. Our studies show that anthracyclines (e.g., epirubicin, daunorubicin, doxorubicin, and idarubicin) consistently suppress both NADPH oxidase-dependent and -independent types of NETosis in human neutrophils, ex vivo. The intercalating property of anthracycline may be enough to alter the transcription initiation and lead NETosis inhibition. Notably, the inhibitory doses of anthracyclines neither suppress the production of reactive oxygen species that are necessary for antimicrobial functions nor induce apoptotic cell death in neutrophils. Therefore, anthracyclines are a major class of drug that suppresses NETosis. The dexrazoxane, a cardioprotective agent, used for limiting the side effects of anthracyclines, neither affect NETosis nor alter the ability of anthracyclines to suppress NETosis. Hence, at correct doses, anthracyclines together with dexrazoxane could be considered as a therapeutic candidate drug for suppressing unwanted NETosis in NET-related diseases. MDPI 2019-09-07 /pmc/articles/PMC6770146/ /pubmed/31500300 http://dx.doi.org/10.3390/cancers11091328 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Khan, Meraj A.
D’Ovidio, Adam
Tran, Harvard
Palaniyar, Nades
Anthracyclines Suppress Both NADPH Oxidase- Dependent and -Independent NETosis in Human Neutrophils
title Anthracyclines Suppress Both NADPH Oxidase- Dependent and -Independent NETosis in Human Neutrophils
title_full Anthracyclines Suppress Both NADPH Oxidase- Dependent and -Independent NETosis in Human Neutrophils
title_fullStr Anthracyclines Suppress Both NADPH Oxidase- Dependent and -Independent NETosis in Human Neutrophils
title_full_unstemmed Anthracyclines Suppress Both NADPH Oxidase- Dependent and -Independent NETosis in Human Neutrophils
title_short Anthracyclines Suppress Both NADPH Oxidase- Dependent and -Independent NETosis in Human Neutrophils
title_sort anthracyclines suppress both nadph oxidase- dependent and -independent netosis in human neutrophils
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770146/
https://www.ncbi.nlm.nih.gov/pubmed/31500300
http://dx.doi.org/10.3390/cancers11091328
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