Dynamin inhibition causes context-dependent cell death of leukemia and lymphoma cells.
Animals
Apoptosis
/ genetics
Bone Marrow Cells
/ metabolism
Caspases
/ blood
Cell Cycle
/ genetics
Cell Death
/ genetics
Cell Line, Tumor
Child
Dynamins
/ antagonists & inhibitors
Endocytosis
/ genetics
Flow Cytometry
Heterografts
Humans
Mice
Pediatrics
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/ blood
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2021
2021
Historique:
received:
19
03
2021
accepted:
28
06
2021
entrez:
7
9
2021
pubmed:
8
9
2021
medline:
17
11
2021
Statut:
epublish
Résumé
Current chemotherapy for treatment of pediatric acute leukemia, although generally successful, is still a matter of concern due to treatment resistance, relapses and life-long side effects for a subset of patients. Inhibition of dynamin, a GTPase involved in clathrin-mediated endocytosis and regulation of the cell cycle, has been proposed as a potential anti-cancer regimen, but the effects of dynamin inhibition on leukemia cells has not been extensively addressed. Here we adopted single cell and whole-population analysis by flow cytometry and live imaging, to assess the effect of dynamin inhibition (Dynasore, Dyngo-4a, MitMAB) on pediatric acute leukemia cell lines (CCRF-CEM and THP-1), human bone marrow biopsies from patients diagnosed with acute lymphoblastic leukemia (ALL), as well as in a model of lymphoma (EL4)-induced tumor growth in mice. All inhibitors suppressed proliferation and induced pronounced caspase-dependent apoptotic cell death in CCRF-CEM and THP-1 cell lines. However, the inhibitors showed no effect on bone marrow biopsies, and did not prevent EL4-induced tumor formation in mice. We conclude that dynamin inhibition affects highly proliferating human leukemia cells. These findings form a basis for evaluation of the potential, and constraints, of employing dynamin inhibition in treatment strategies against leukemia and other malignancies.
Identifiants
pubmed: 34492077
doi: 10.1371/journal.pone.0256708
pii: PONE-D-21-09071
pmc: PMC8423305
doi:
Substances chimiques
Caspases
EC 3.4.22.-
Dynamins
EC 3.6.5.5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0256708Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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