| Full text | |
| Author(s): |
Hirakata, Camila
[1]
;
Lima, Keli
[1]
;
De Almeida, Bruna Oliveira
[1]
;
De Miranda, Livia Bassani Lins
[1]
;
Florencio, Katharine Gurgel Dias
[2]
;
Furtado, Luciana Costa
[1]
;
Costa-Lotufo, Leticia Veras
[1]
;
Machado-Neto, Joao Agostinho
[1]
Total Authors: 8
|
| Affiliation: | [1] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, 1524 Ave Prof Lineu Prestes, BR-05508900 Sao Paulo - Brazil
[2] Univ Fed Ceara, Drug Res & Dev Ctr, Dept Physiol & Pharmacol, BR-60440900 Fortaleza, Ceara - Brazil
Total Affiliations: 2
|
| Document type: | Journal article |
| Source: | Oncology Letters; v. 22, n. 2 AUG 2021. |
| Web of Science Citations: | 0 |
| Abstract | |
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 mu M) 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. (AU) | |
| FAPESP's process: | 15/17177-6 - Integrative approach on the sustainable prospection of marine natural products: from diversity to anticancer compounds |
| Grantee: | Leticia Veras Costa Lotufo |
| Support Opportunities: | BIOTA-FAPESP Program - Thematic Grants |
| FAPESP's process: | 18/19372-9 - Investigation of the effect of potential Stathmin 1 inhibitors obtained by chemoinformatics on the phenotype of acute leukemias |
| Grantee: | Jorge Antonio Elias Godoy Carlos |
| Support Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 19/23864-7 - Comprehensive analysis of genomic data for identification and validation of novel therapeutic targets involved in cellular cytoskeleton regulation in acute Leukemia |
| Grantee: | João Agostinho Machado Neto |
| Support Opportunities: | Regular Research Grants |