Number of the records: 1
New Insights into Tolytoxin Effect in Human Cancer Cells: Apoptosis Induction and the Relevance of Hydroxyl Substitution of Its Macrolide Cycle on Compound Potency
- 1.
SYSNO ASEP 0553487 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title New Insights into Tolytoxin Effect in Human Cancer Cells: Apoptosis Induction and the Relevance of Hydroxyl Substitution of Its Macrolide Cycle on Compound Potency Author(s) Delawská, Kateřina (MBU-M) ORCID
Divoká, Petra (MBU-M)
Sedlák, David (UMG-J) RID
Kuzma, Marek (MBU-M) ORCID, RID
Saurav, Kumar (MBU-M) ORCID
Macho, Markéta (MBU-M) ORCID
Steinbach, G. (HU)
Hrouzek, Pavel (MBU-M) ORCIDArticle number e202100489 Source Title Chembiochem. - : Wiley - ISSN 1439-4227
Roč. 23, č. 1 (2022)Number of pages 5 s. Language eng - English Country DE - Germany Keywords actin ; binding ; scytophycins ; agents ; actin disruption ; apoptosis ; cancer ; scytophycines ; tolytoxin Subject RIV CE - Biochemistry OECD category Biochemistry and molecular biology Subject RIV - cooperation Institute of Molecular Genetics R&D Projects GF21-05649K GA ČR - Czech Science Foundation (CSF) LO1416 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LM2018130 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Limited access Institutional support MBU-M - RVO:61388971 ; UMG-J - RVO:68378050 UT WOS 000728404200001 EID SCOPUS 85120791599 DOI 10.1002/cbic.202100489 Annotation 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. Workplace Institute of Microbiology Contact Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Year of Publishing 2023 Electronic address https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202100489
Number of the records: 1