Reversine exerts cytotoxic effects through multiple cell death mechanisms in acute lymphoblastic leukemia.
Apoptosis
/ drug effects
Aurora Kinase B
/ metabolism
Autophagy
/ drug effects
Cell Cycle Checkpoints
/ drug effects
Cell Death
/ drug effects
Cell Line, Tumor
Cell Proliferation
/ drug effects
Clone Cells
DNA Damage
Humans
Morpholines
/ pharmacology
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/ enzymology
Purines
/ pharmacology
Acute lymphoblastic leukemia
Aurora kinases
Cell death
Reversine
Journal
Cellular oncology (Dordrecht)
ISSN: 2211-3436
Titre abrégé: Cell Oncol (Dordr)
Pays: Netherlands
ID NLM: 101552938
Informations de publication
Date de publication:
Dec 2020
Dec 2020
Historique:
accepted:
22
07
2020
pubmed:
29
8
2020
medline:
6
8
2021
entrez:
29
8
2020
Statut:
ppublish
Résumé
Acute lymphoblastic leukemia (ALL) is an aggressive hematological cancer with limited therapeutic options for adult patients. Aurora kinases have drawn attention as potential targets in hematological neoplasms due to their high expression and biological functions. Aurora kinase A (AURKA) and AURKB are essential for a successful mitosis, acting in spindle mitotic organization and cytokinesis. Reversine is a synthetic purine analog that acts as a multi-kinase inhibitor with anti-neoplastic activity by targeting AURKA and AURKB. ALL patient gene expression data were retrieved from the Amazonia! For functional assays, Jurkat (T-ALL) and Namalwa (B-ALL) cells were exposed to increasing concentrations of reversine and submitted to various cellular and molecular assays. We found that AURKB expression was higher in ALL patient samples compared to normal lymphocytes (p < 0.0001). The ALL cell lines tested displayed aberrant AURKA and AURKB expression. In Jurkat and Namalwa cells, reversine reduced cell viability in a dose- and time-dependent manner (p < 0.05). Reversine also significantly reduced the viability of primary ALL cells. Reversine induced apoptosis and autophagy, and reduced cell proliferation in both cell lines (p < 0.05). Mitotic catastrophe markers, including cell cycle arrest at G From our data we conclude that reversine reduces the viability of ALL cells by triggering multiple cell death mechanisms, including apoptosis, mitotic catastrophe, and autophagy. Our findings highlight reversine as a potential anticancer agent for ALL.
Identifiants
pubmed: 32857324
doi: 10.1007/s13402-020-00551-3
pii: 10.1007/s13402-020-00551-3
doi:
Substances chimiques
Morpholines
0
Purines
0
Aurora Kinase B
EC 2.7.11.1
2-(4-morpholinoanilino)-6-cyclohexylaminopurine
Z499CLJ023
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1191-1201Subventions
Organisme : Fundação de Amparo à Pesquisa do Estado de São Paulo
ID : 2017/24993-0
Organisme : Fundação de Amparo à Pesquisa do Estado de São Paulo
ID : 2018/19372-9
Organisme : Fundação de Amparo à Pesquisa do Estado de São Paulo
ID : 2015/17177-6
Organisme : Conselho Nacional de Desenvolvimento Científico e Tecnológico
ID : 402587/2016-2
Organisme : Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
ID : #
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