Targeting glioma cells by antineoplastic activity of reversine.
apoptosis
aurora kinases
glioblastoma
gliomas
reversine
Journal
Oncology letters
ISSN: 1792-1074
Titre abrégé: Oncol Lett
Pays: Greece
ID NLM: 101531236
Informations de publication
Date de publication:
Aug 2021
Aug 2021
Historique:
received:
03
04
2021
accepted:
02
06
2021
entrez:
30
6
2021
pubmed:
1
7
2021
medline:
1
7
2021
Statut:
ppublish
Résumé
Gliomas are the most common type of primary central nervous system tumors and despite great advances in understanding the molecular basis of the disease very few new therapies have been developed. Reversine, a synthetic purine analog, is a multikinase inhibitor that targets aurora kinase A (AURKA) and aurora kinase B (AURKB). In gliomas, a high expression of AURKA or AURKB is associated with a malignant phenotype and a poor prognosis. The present study investigated reversine-related cellular and molecular antiglioma effects in HOG, T98G and U251MG cell lines. Gene and protein expression were assessed by reverse transcription-quantitative PCR and western blotting, respectively. For functional assays, human glioma cell lines (HOG, T98G and U251MG) were exposed to increasing concentrations of reversine (0.4-50 µM) and subjected to various cellular and molecular assays. Reversine reduced the viability and clonogenicity in a dose- and/or time-dependent manner in all glioma cells, with HOG (high AURKB-expression) and T98G (high AURKA-expression) cells being more sensitive compared with U251MG cells (low AURKA- and AURKB-expression). Notably, HOG cells presented higher levels of polyploidy, while T98G presented multiple mitotic spindles, which is consistent with the main regulatory functions of AURKB and AURKA, respectively. In molecular assays, reversine reduced AURKA and/or AURKB expression/activity and increased DNA damage and apoptosis markers, but autophagy-related proteins were not modulated. In conclusion, reversine potently induced mitotic catastrophe and apoptosis in glioma cells and higher basal levels of aurora kinases and genes responsive to DNA damage and may predict improved antiglioma responses to the drug. Reversine may be a potential novel drug in the antineoplastic arsenal against gliomas.
Identifiants
pubmed: 34188712
doi: 10.3892/ol.2021.12871
pii: OL-0-0-12871
pmc: PMC8227489
doi:
Types de publication
Journal Article
Langues
eng
Pagination
610Informations de copyright
Copyright: © Hirakata et al.
Déclaration de conflit d'intérêts
The authors declare that they have no competing interests.
Références
Mol Cancer Ther. 2015 Feb;14(2):419-28
pubmed: 25522764
Proteins. 2016 Dec;84(12):1761-1766
pubmed: 27699881
Anticancer Drugs. 2018 Jan;29(1):29-39
pubmed: 28984683
EMBO J. 2015 Apr 1;34(7):856-80
pubmed: 25712477
Onco Targets Ther. 2018 Feb 26;11:1025-1035
pubmed: 29520153
Cancer Cell Int. 2019 Jun 18;19:166
pubmed: 31244554
Leuk Res. 2016 Sep;48:26-31
pubmed: 27447890
Biotechniques. 2003 Feb;34(2):374-8
pubmed: 12613259
J Biomed Sci. 2012 Jan 27;19:9
pubmed: 22283874
Cell. 2013 Oct 10;155(2):462-77
pubmed: 24120142
Cell Oncol (Dordr). 2020 Dec;43(6):1191-1201
pubmed: 32857324
Oncotarget. 2017 Apr 4;8(14):23937-23954
pubmed: 28147341
Methods. 2001 Dec;25(4):402-8
pubmed: 11846609
Genes Genomics. 2019 Jun;41(6):657-665
pubmed: 30953339
Sci Rep. 2018 Aug 7;8(1):11821
pubmed: 30087398
Cell. 2009 Feb 6;136(3):473-84
pubmed: 19203582
Nat Med. 2013 Feb;19(2):202-8
pubmed: 23291630
Cell Div. 2018 Sep 19;13:7
pubmed: 30250494
Mol Cancer Ther. 2008 May;7(5):1140-9
pubmed: 18483302
Eur J Med Chem. 2017 Nov 10;140:1-19
pubmed: 28918096
J Neurosurg Sci. 2019 Apr;63(2):179-186
pubmed: 30421895
Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19512-7
pubmed: 18040043
Breast Cancer. 2014 May;21(3):358-69
pubmed: 22926505
Cancers (Basel). 2020 Sep 03;12(9):
pubmed: 32899427
Curr Cancer Drug Targets. 2018;18(10):914-928
pubmed: 29521234
Crit Rev Oncog. 2011;16(1-2):129-40
pubmed: 22150313
Neuro Oncol. 2020 Oct 30;22(12 Suppl 2):iv1-iv96
pubmed: 33123732
Acta Histochem. 2001 Jul;103(3):241-51
pubmed: 11482370
PLoS One. 2016 Jul 06;11(7):e0158587
pubmed: 27385117
Arch Oral Biol. 2019 Dec;108:104530
pubmed: 31470141
N Engl J Med. 2014 Feb 20;370(8):699-708
pubmed: 24552317
Cell Cycle. 2012 Feb 1;11(3):489-502
pubmed: 22274399
Cytotechnology. 2013 Aug;65(4):643-53
pubmed: 23475158
Dtsch Arztebl Int. 2018 May 21;115(20-21):356-364
pubmed: 29914619
Pathol Res Pract. 2019 Nov;215(11):152617
pubmed: 31563286
Biomed Pharmacother. 2012 Dec;66(8):642-7
pubmed: 23089471
Pharm Res. 2012 Jul;29(7):1990-2005
pubmed: 22477067
World J Stem Cells. 2020 Jun 26;12(6):481-487
pubmed: 32742565
Clin Transl Oncol. 2009 Dec;11(12):787-98
pubmed: 20045785
Adv Exp Med Biol. 2013;793:1-19
pubmed: 24104470
Recent Pat Anticancer Drug Discov. 2010 Nov;5(3):219-41
pubmed: 20524930
Biomedicines. 2021 Mar 22;9(3):
pubmed: 33810154
Sci Rep. 2019 Jul 9;9(1):9895
pubmed: 31289316
Cancer Chemother Pharmacol. 2014 May;73(5):983-90
pubmed: 24627220
Br J Cancer. 2003 Nov 3;89(9):1802-11
pubmed: 14583787
Perspect Biol Med. 1990 Autumn;34(1):109-23
pubmed: 2274399
Acta Neuropathol. 2016 Jun;131(6):803-20
pubmed: 27157931
Curr Med Chem. 2020;27(21):3448-3462
pubmed: 30605049
Neuro Oncol. 2018 Nov 9;20(suppl_7):vii6-vii16
pubmed: 29850889
N Engl J Med. 2015 Jun 25;372(26):2481-98
pubmed: 26061751
Nat Rev Cancer. 2005 Jan;5(1):42-50
pubmed: 15630414
Int J Oncol. 2019 May;54(5):1875-1883
pubmed: 30864676
N Engl J Med. 2005 Mar 10;352(10):987-96
pubmed: 15758009