In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 9 ( 2021-9-7), p. e0256708-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0256708
DOI:
10.1371/journal.pone.0256708.g001
DOI:
10.1371/journal.pone.0256708.g002
DOI:
10.1371/journal.pone.0256708.g003
DOI:
10.1371/journal.pone.0256708.g004
DOI:
10.1371/journal.pone.0256708.g005
DOI:
10.1371/journal.pone.0256708.g006
DOI:
10.1371/journal.pone.0256708.g007
DOI:
10.1371/journal.pone.0256708.g008
DOI:
10.1371/journal.pone.0256708.s001
DOI:
10.1371/journal.pone.0256708.s002
DOI:
10.1371/journal.pone.0256708.s003
DOI:
10.1371/journal.pone.0256708.s004
DOI:
10.1371/journal.pone.0256708.s005
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2267670-3
Bookmarklink