| Autor: |
Sales L; aInstitute of Natural Science bDepartment of Cell and Developmental Biology, Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil., de Sousa GR, Ferreira-Silva GÁ, Castro-Gamero AM, Ionta M, de Oliveira JC |
| Jazyk: |
angličtina |
| Zdroj: |
Anti-cancer drugs [Anticancer Drugs] 2017 Mar; Vol. 28 (3), pp. 298-306. |
| DOI: |
10.1097/CAD.0000000000000462 |
| Abstrakt: |
T-acute lymphoblastic leukemia (T-ALL) is an aggressive hematological cancer that arises from the malignant transformation of T-cell progenitors. Despite the significant progress in current treatment, challenges remain the lifelong morbidity after current chemotherapy regimens and postrelapse survival. In addition, patients with T-ALL have inferior outcomes compared with those with B-cell precursor; consequently, novel therapeutic approaches are still necessary to improve the outcome in this cohort. YM155 is an imidazolium derivative originally discovered as a suppressant of survivin expression. It has been reported that YM155 has potent antiproliferative activity on a variety of human cancer cell lines; however, its effects in T-ALL cells have been underexplored. The aim of the present study was to examine the effects of YM155 on p53-deficient T-ALL cell lines, JURKAT and CCRF-CEM. Resazurin dye was used to evaluate cell viability. Colony formation was observed in MethoCult methylcellulose medium. Apoptotic cells were detected by flow cytometry (annexin V labeling and TUNEL assay). Cell cycle analysis was carried out by DNA quantification in flow cytometry. DNA damage was assessed using a comet assay and the survivin expression profile was evaluated by real-time PCR and immunoblotting. YM155 treatment decreased cell viability and clonogenicity capacity of T-ALL cells, increased the apoptosis index and DNA damage, and altered the cell cycle dynamic, independent of survivin inhibition. Taken together, the data reinforce that YM155 may be useful as a therapeutic possibility to combat leukemia. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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