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New Insights into Tolytoxin Effect in Human Cancer Cells: Apoptosis Induction and the Relevance of Hydroxyl Substitution of Its Macrolide Cycle on Compound Potency
K. Delawská, P. Divoká, D. Sedlák, M. Kuzma, K. Saurav, M. Macho, G. Steinbach, P. Hrouzek
Language English Country Germany
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
21-05649K
Czech Grant Agency (Discovery of promising chemotherapeutic candidates in cyanobacteria
68378050-KAV-NPUI
Ministry of Education, Youth and Sports of the Czech Republic
LM2018130
National infrastructure for chemical biology
41
Cross-Border cooperation Czech-Bavaria
GINOP-2.3.2-15-2016-00001
Cross-Border cooperation Czech-Bavaria
Medical University Innsbruck
- MeSH
- Apoptosis drug effects MeSH
- Hydroxides chemistry pharmacology MeSH
- Humans MeSH
- Macrolides chemistry pharmacology MeSH
- Mitochondria drug effects metabolism MeSH
- Cell Line, Tumor MeSH
- Cell Proliferation drug effects MeSH
- Antineoplastic Agents chemistry pharmacology MeSH
- Pyrans chemistry pharmacology MeSH
- Drug Screening Assays, Antitumor MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Scytophycins, including tolytoxin, represent a class of actin disrupting macrolides with strong antiproliferative effects on human cells. Despite intense research, little attention has been paid to scytophycin-induced cell death or the structural features affecting its potency. We show that tolytoxin and its natural analogue, 7-O-methylscytophycin B, lacking the hydroxyl substitution in its macrolactone ring, differ substantially in their cytotoxic effect. Both compounds increase the level of caspases 3/7, which are the main executioner proteases during apoptosis, in HeLa wild-type (WT) cells. However, no caspase activity was detected in HeLa cells lacking Bax/Bak proteins crucial for caspase activation via the mitochondrial pathway. Obtained data strongly suggests that scytophycins are capable of inducing mitochondria-dependent apoptosis. These findings encourage further research in structure-activity relationships in scytophycins and highlight the potential of these compounds in targeted drug delivery.
References provided by Crossref.org
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