The pterocarpanquinone LQB118 compound induces apoptosis of cytarabineresistant acute myeloid leukemia cells.
Int J Oncol
; 58(6)2021 06.
Article
in En
| MEDLINE
| ID: mdl-33786613
ABSTRACT
Acute myeloid leukemia (AML) is a complex hematological disorder characterized by blockage of differentiation and high proliferation rates of myeloid progenitors. Anthracycline and cytarabinebased therapy has remained the standard treatment for AML over the last four decades. Although this treatment strategy has increased survival rates, patients often develop resistance to these drugs. Despite efforts to understand the mechanisms underlying cytarabine resistance, there have been few advances in the field. The present study developed an in vitro AML cell line model resistant to cytarabine (HL60R), and identified chromosomal aberrations by karyotype evaluation and potential molecular mechanisms underlying chemoresistance. Cytarabine decreased cell viability, as determined by MTT assay, and induced cell death and cell cycle arrest in the parental HL60 cell line, as revealed by Annexin V/propidium iodide (PI) staining and PI DNA incorporation, respectively, whereas no change was observed in the HL60R cell line. In addition, the HL60R cell line exhibited a higher tumorigenic capacity in vivo compared with the parental cell line. Notably, no reduction in tumor volume was detected in mice treated with cytarabine and inoculated with HL60R cells. In addition, western blotting revealed that the protein expression levels of Bcl2, Xlinked inhibitor of apoptosis protein (XIAP) and cMyc were upregulated in HL60R cells compared with those in HL60 cells, along with predominant nuclear localization of the p50 and p65 subunits of NFκB in HL60R cells. Furthermore, the antitumor effect of LQB118 pterocarpanquinone was investigated; this compound induced apoptosis, a reduction in cell viability and a decrease in XIAP expression in cytarabineresistant cells. Taken together, these data indicated that acquired cytarabine resistance in AML was a multifactorial process, involving chromosomal aberrations, and differential expression of apoptosis and cell proliferation signaling pathways. Furthermore, LQB118 could be a potential alternative therapeutic approach to treat cytarabineresistant leukemia cells.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Leukemia, Myeloid, Acute
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Chromosome Aberrations
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Naphthoquinones
/
Pterocarpans
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Int J Oncol
Journal subject:
NEOPLASIAS
Year:
2021
Document type:
Article
Affiliation country:
Brazil