Jaspine B Hydrochloride-induced Apoptosis in HeLa Cells Is Associated With Disrupted Sphingolipid Metabolism and Ceramide Overload.


Journal

Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988

Informations de publication

Date de publication:
Jun 2021
Historique:
received: 01 04 2021
revised: 30 04 2021
accepted: 04 05 2021
entrez: 4 6 2021
pubmed: 5 6 2021
medline: 22 6 2021
Statut: ppublish

Résumé

A series of experiments on HeLa cells were conducted to provide new information concerning the anti-cancer properties of jaspine B hydrochloride (JBH). HeLa cells treated with 0.5 μmol/l JBH for 24, 48, and 72 h underwent flow cytometric analysis of the cell cycle, and measurement of phosphatidylserine externalization, mitochondrial membrane potential (MMP), casp-3 activation, cleavage of PARP, ceramide levels, aSMase activity, and Bcl-2 release. nSMase activity was measured by a colorimetric assay. Gene expression was determined by qRT-PCR. Immunocytochemistry was performed to detect p21 and p27 expression. JBH-induced apoptosis in HeLa cells associated with externalization of phosphatidylserine, reduced MMP, activation of casp-3, and cleavage of PARP as well as up-regulation of TNF-α, FasL, and casp-8. Significant increase in nSMase activity, ceramide levels, Bcl-2 release (predominantly in the inactive form), and pro-apoptotic nuclear localization of p21 and p27 were also detected. JBH-induced apoptosis in HeLa cells is associated with disrupted sphingolipid homeostasis resulting in increased ceramide levels.

Sections du résumé

BACKGROUND/AIM OBJECTIVE
A series of experiments on HeLa cells were conducted to provide new information concerning the anti-cancer properties of jaspine B hydrochloride (JBH).
MATERIALS AND METHODS METHODS
HeLa cells treated with 0.5 μmol/l JBH for 24, 48, and 72 h underwent flow cytometric analysis of the cell cycle, and measurement of phosphatidylserine externalization, mitochondrial membrane potential (MMP), casp-3 activation, cleavage of PARP, ceramide levels, aSMase activity, and Bcl-2 release. nSMase activity was measured by a colorimetric assay. Gene expression was determined by qRT-PCR. Immunocytochemistry was performed to detect p21 and p27 expression.
RESULTS RESULTS
JBH-induced apoptosis in HeLa cells associated with externalization of phosphatidylserine, reduced MMP, activation of casp-3, and cleavage of PARP as well as up-regulation of TNF-α, FasL, and casp-8. Significant increase in nSMase activity, ceramide levels, Bcl-2 release (predominantly in the inactive form), and pro-apoptotic nuclear localization of p21 and p27 were also detected.
CONCLUSION CONCLUSIONS
JBH-induced apoptosis in HeLa cells is associated with disrupted sphingolipid homeostasis resulting in increased ceramide levels.

Identifiants

pubmed: 34083278
pii: 41/6/2875
doi: 10.21873/anticanres.15069
doi:

Substances chimiques

Ceramides 0
Sphingolipids 0
pachastrissamine 0
Sphingosine NGZ37HRE42

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2875-2883

Informations de copyright

Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Auteurs

Alexandra Bogdanova (A)

Department of Pharmacology, Faculty of Medicine, P.J. Šafárik University, Košice, Slovak Republic.

Martin Kello (M)

Department of Pharmacology, Faculty of Medicine, P.J. Šafárik University, Košice, Slovak Republic.

Alexandra Macejova (A)

Department of Pharmacology, Faculty of Medicine, P.J. Šafárik University, Košice, Slovak Republic.

Natalia Nosalova (N)

Department of Pharmacology, Faculty of Medicine, P.J. Šafárik University, Košice, Slovak Republic.

Peter Petik (P)

Department of Pathology, Faculty of Medicine, P.J. Šafárik University, Košice, Slovak Republic.

Peter Takac (P)

Department of Pharmacology and Toxicology, University of Veterinary Medicine and Pharmacy, Košice, Slovak Republic.

Miroslava Martinkova (M)

Institute of Chemical Sciences, Department of Organic Chemistry, Faculty of Science, P.J. Šafárik University, Košice, Slovak Republic.

Eva Mezeiova (E)

Institute of Chemical Sciences, Department of Organic Chemistry, Faculty of Science, P.J. Šafárik University, Košice, Slovak Republic.

Ladislav Mirossay (L)

Department of Pharmacology, Faculty of Medicine, P.J. Šafárik University, Košice, Slovak Republic.

Peter Gal (P)

Center of Clinical and Preclinical Research MEDIPARK, Faculty of Medicine, P.J. Šafárik University, Košice, Slovak Republic.
Department of Biomedical Research, East-Slovak Institute of Cardiovascular Diseases, Inc., Košice, Slovak Republic.
Prague Burn Center, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
Department of Pharmacognosy and Botany, Faculty of Pharmacy, Comenius University, Bratislava, Slovak Republic.

Martina Bago Pilatova (MB)

Department of Pharmacology, Faculty of Medicine, P.J. Šafárik University, Košice, Slovak Republic; martina.pilatova@upjs.sk.

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Classifications MeSH