New Insights into Tolytoxin Effect in Human Cancer Cells: Apoptosis Induction and the Relevance of Hydroxyl Substitution of Its Macrolide Cycle on Compound Potency

0553487 - MBÚ 2023 RIV DE eng J - Journal Article
Delawská, Kateřina - Divoká, Petra - Sedlák, David - Kuzma, Marek - Saurav, Kumar - Macho, Markéta - Steinbach, G. - Hrouzek, Pavel
New Insights into Tolytoxin Effect in Human Cancer Cells: Apoptosis Induction and the Relevance of Hydroxyl Substitution of Its Macrolide Cycle on Compound Potency.
Chembiochem. Roč. 23, č. 1 (2022), č. článku e202100489. ISSN 1439-4227. E-ISSN 1439-7633
R&D Projects: GA ČR(CZ) GF21-05649K; GA MŠMT(CZ) LO1416; GA MŠMT(CZ) LM2018130
EU Projects: European Commission(XE) Interreg 41 Czech-Bavaria
Institutional support: RVO:61388971 ; RVO:68378050
Keywords : actin * binding * scytophycins * agents * actin disruption * apoptosis * cancer * scytophycines * tolytoxin
OECD category: Biochemistry and molecular biology
Impact factor: 3.2, year: 2022
Method of publishing: Limited access
https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202100489

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.
Permanent Link: http://hdl.handle.net/11104/0330344