Cold Atmospheric Plasma Triggers Apoptosis via the Unfolded Protein Response in Melanoma Cells.

apoptosis ceramide cold atmospheric plasma melanoma unfolded protein response

Journal

Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829

Informations de publication

Date de publication:
07 Feb 2023
Historique:
received: 13 01 2023
revised: 02 02 2023
accepted: 04 02 2023
entrez: 25 2 2023
pubmed: 26 2 2023
medline: 26 2 2023
Statut: epublish

Résumé

Cold atmospheric plasma (CAP) describes a partially ionized gas carrying large amounts of reactive oxygen (ROS) and nitrogen species (RNS). Numerous studies reported strong antitumor activity of CAP, thus rendering it a promising approach for tumor therapy. Although several cellular mechanisms of its cytotoxicity were identified in recent years, the exact molecular effects and contributing signaling pathways are yet to be discovered. We discovered a strong activation of unfolded protein response (UPR) after CAP treatment with increased C/EBP homologous protein (CHOP) expression, which was mainly caused by protein misfolding and calcium loss in the endoplasmic reticulum. In addition, both ceramide level and ceramide metabolism were reduced after CAP treatment, which was then linked to the UPR activation. Pharmacological inhibition of ceramide metabolism resulted in sensitization of melanoma cells for CAP both in vitro and ex vivo. This study identified a novel mechanism of CAP-induced apoptosis in melanoma cells and thereby contributes to its potential application in tumor therapy.

Identifiants

pubmed: 36831408
pii: cancers15041064
doi: 10.3390/cancers15041064
pmc: PMC9954601
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Deutsche Forschungsgemeinschaft
ID : BO1573

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Auteurs

Tom Zimmermann (T)

Institute of Biochemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.

Sebastian Staebler (S)

Institute of Biochemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.

R Verena Taudte (RV)

Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg, 91054 Erlangen, Germany.
Core Facility Metabolomics/Mass Spectrometry, Philipps University Marburg, 35043 Marburg, Germany.

Sumeyya Ünüvar (S)

Institute of Biochemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.

Sabine Grösch (S)

Institute of Clinical Pharmacology, Faculty of Medicine, Goethe University Frankfurt, 60590 Frankfurt, Germany.

Stephanie Arndt (S)

Department of Dermatology, University Hospital of Regensburg, 93053 Regensburg, Germany.

Sigrid Karrer (S)

Department of Dermatology, University Hospital of Regensburg, 93053 Regensburg, Germany.

Martin F Fromm (MF)

Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg, 91054 Erlangen, Germany.

Anja-Katrin Bosserhoff (AK)

Institute of Biochemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
Comprehensive Cancer Center (CCC) Erlangen-EMN, 91054 Erlangen, Germany.

Classifications MeSH