The Widely Used Antihelmintic Drug Albendazole is a Potent Inducer of Loss of Heterozygosity.
albendazole
aneuploidy
cancer predisposition
helminth
loss of heterozygosity (LOH)
spindle poison
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2021
2021
Historique:
received:
19
08
2020
accepted:
11
01
2021
entrez:
8
3
2021
pubmed:
9
3
2021
medline:
9
3
2021
Statut:
epublish
Résumé
The antihelmintic drug ABZ and its metabolites belong to the chemical family of benzimidazoles (BZM) that act as potent tubulin polymerization inhibitors, suggesting a potential re-direction of BZMs for cancer therapy. Applying UV-Vis spectrometry we here demonstrate ABZ as a DNA intercalator. This insight led us to determine the primary mode of ABZ action in mammalian cells. As revealed by RNA sequencing, ABZ did neither grossly affect replication as analyzed by survival and replication stress signaling, nor the transcriptome. Actually, unbiased transcriptome analysis revealed a marked cell cycle signature in ABZ exposed cells. Indeed, short-term exposure to ABZ arrested mammalian cells in G2/M cell cycle stages associated with frequent gains and losses of chromatin. Cellular analyses revealed ABZ as a potent mammalian spindle poison for normal and malignant cells, explaining the serious chromosome segregation defects. Since chromosomal aberrations promote both cancer development and cell death, we determined if besides its general cytotoxicity, ABZ could predispose to tumor development. As measured by loss of heterozygosity (LOH)
Identifiants
pubmed: 33679394
doi: 10.3389/fphar.2021.596535
pii: 596535
pmc: PMC7935534
doi:
Types de publication
Journal Article
Langues
eng
Pagination
596535Informations de copyright
Copyright © 2021 Will Castro, Pieters, Alemdehy, Aslam, Buoninfante, Raaijmakers, Pilzecker, van den Berk, te Riele, Medema, Pedrosa and Jacobs.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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