Jaspine B Hydrochloride-induced Apoptosis in HeLa Cells Is Associated With Disrupted Sphingolipid Metabolism and Ceramide Overload
Language English Country Greece Media print
Document type Journal Article
PubMed
34083278
DOI
10.21873/anticanres.15069
PII: 41/6/2875
Knihovny.cz E-resources
- Keywords
- Jaspine B, antiproliferative activity, apoptosis, cervical cancer, marine derivatives,
- MeSH
- Apoptosis drug effects MeSH
- Ceramides metabolism MeSH
- HeLa Cells MeSH
- Humans MeSH
- Cell Proliferation drug effects MeSH
- Sphingolipids metabolism MeSH
- Sphingosine analogs & derivatives pharmacology MeSH
- Signal Transduction drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Ceramides MeSH
- pachastrissamine MeSH Browser
- Sphingolipids MeSH
- Sphingosine MeSH
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.
Department of Pathology Faculty of Medicine P J Šafárik University Košice Slovak Republic
Department of Pharmacology Faculty of Medicine P J Šafárik University Košice Slovak Republic
Department of Pharmacology Faculty of Medicine P J Šafárik University Košice Slovak Republic;
Prague Burn Center 3rd Faculty of Medicine Charles University Prague Czech Republic
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