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Research ArticleExperimental Studies

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

ALEXANDRA BOGDANOVA, MARTIN KELLO, ALEXANDRA MACEJOVA, NATALIA NOSALOVA, PETER PETIK, PETER TAKAC, MIROSLAVA MARTINKOVA, EVA MEZEIOVA, LADISLAV MIROSSAY, PETER GAL and MARTINA BAGO PILATOVA
Anticancer Research June 2021, 41 (6) 2875-2883; DOI: https://doi.org/10.21873/anticanres.15069
ALEXANDRA BOGDANOVA
1Department of Pharmacology, Faculty of Medicine, P.J. Šafárik University, Košice, Slovak Republic;
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MARTIN KELLO
1Department of Pharmacology, Faculty of Medicine, P.J. Šafárik University, Košice, Slovak Republic;
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ALEXANDRA MACEJOVA
1Department of Pharmacology, Faculty of Medicine, P.J. Šafárik University, Košice, Slovak Republic;
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NATALIA NOSALOVA
1Department of Pharmacology, Faculty of Medicine, P.J. Šafárik University, Košice, Slovak Republic;
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PETER PETIK
2Department of Pathology, Faculty of Medicine, P.J. Šafárik University, Košice, Slovak Republic;
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PETER TAKAC
3Department of Pharmacology and Toxicology, University of Veterinary Medicine and Pharmacy, Košice, Slovak Republic;
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MIROSLAVA MARTINKOVA
4Institute of Chemical Sciences, Department of Organic Chemistry, Faculty of Science, P.J. Šafárik University, Košice, Slovak Republic;
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EVA MEZEIOVA
4Institute of Chemical Sciences, Department of Organic Chemistry, Faculty of Science, P.J. Šafárik University, Košice, Slovak Republic;
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LADISLAV MIROSSAY
1Department of Pharmacology, Faculty of Medicine, P.J. Šafárik University, Košice, Slovak Republic;
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PETER GAL
5Center of Clinical and Preclinical Research MEDIPARK, Faculty of Medicine, P.J. Šafárik University, Košice, Slovak Republic;
6Department of Biomedical Research, East-Slovak Institute of Cardiovascular Diseases, Inc., Košice, Slovak Republic;
7Prague Burn Center, Third Faculty of Medicine, Charles University, Prague, Czech Republic;
8Department of Pharmacognosy and Botany, Faculty of Pharmacy, Comenius University, Bratislava, Slovak Republic
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MARTINA BAGO PILATOVA
1Department of Pharmacology, Faculty of Medicine, P.J. Šafárik University, Košice, Slovak Republic;
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  • For correspondence: martina.pilatova@upjs.sk
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Abstract

Background/Aim: 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: 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: 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: JBH-induced apoptosis in HeLa cells is associated with disrupted sphingolipid homeostasis resulting in increased ceramide levels.

Key Words:
  • Jaspine B
  • antiproliferative activity
  • apoptosis
  • marine derivatives
  • cervical cancer
  • Received April 1, 2021.
  • Revision received April 30, 2021.
  • Accepted May 4, 2021.
  • Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Research: 41 (6)
Anticancer Research
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June 2021
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Jaspine B Hydrochloride-induced Apoptosis in HeLa Cells Is Associated With Disrupted Sphingolipid Metabolism and Ceramide Overload
ALEXANDRA BOGDANOVA, MARTIN KELLO, ALEXANDRA MACEJOVA, NATALIA NOSALOVA, PETER PETIK, PETER TAKAC, MIROSLAVA MARTINKOVA, EVA MEZEIOVA, LADISLAV MIROSSAY, PETER GAL, MARTINA BAGO PILATOVA
Anticancer Research Jun 2021, 41 (6) 2875-2883; DOI: 10.21873/anticanres.15069

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Jaspine B Hydrochloride-induced Apoptosis in HeLa Cells Is Associated With Disrupted Sphingolipid Metabolism and Ceramide Overload
ALEXANDRA BOGDANOVA, MARTIN KELLO, ALEXANDRA MACEJOVA, NATALIA NOSALOVA, PETER PETIK, PETER TAKAC, MIROSLAVA MARTINKOVA, EVA MEZEIOVA, LADISLAV MIROSSAY, PETER GAL, MARTINA BAGO PILATOVA
Anticancer Research Jun 2021, 41 (6) 2875-2883; DOI: 10.21873/anticanres.15069
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Keywords

  • Jaspine B
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