New Insights into Tolytoxin Effect in Human Cancer Cells: Apoptosis Induction and the Relevance of Hydroxyl Substitution of Its Macrolide Cycle on Compound Potency.
actin disruption
apoptosis
cancer
scytophycines
tolytoxin
Journal
Chembiochem : a European journal of chemical biology
ISSN: 1439-7633
Titre abrégé: Chembiochem
Pays: Germany
ID NLM: 100937360
Informations de publication
Date de publication:
05 01 2022
05 01 2022
Historique:
revised:
16
11
2021
received:
16
09
2021
pubmed:
26
11
2021
medline:
22
2
2022
entrez:
25
11
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34821450
doi: 10.1002/cbic.202100489
doi:
Substances chimiques
Antineoplastic Agents
0
Hydroxides
0
Macrolides
0
Pyrans
0
tolytoxin
127999-44-4
hydroxide ion
9159UV381P
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e202100489Subventions
Organisme : Czech Grant Agency (Discovery of promising chemotherapeutic candidates in cyanobacteria
ID : 21-05649K
Organisme : Ministry of Education, Youth and Sports of the Czech Republic
ID : 68378050-KAV-NPUI
Organisme : National infrastructure for chemical biology
ID : LM2018130
Organisme : Cross-Border cooperation Czech-Bavaria
ID : 41
Organisme : Cross-Border cooperation Czech-Bavaria
ID : GINOP-2.3.2-15-2016-00001
Organisme : Medical University Innsbruck
Informations de copyright
© 2021 Wiley-VCH GmbH.
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