Predictors of severity and new treatments for bone marrow neoplasias
| Full text | |
| Author(s): |
Vieira Torquato, Heron F.
;
Ribeiro-Filho, Antonio C.
;
Buri, Marcus V.
;
Araujo Junior, Roberto T.
;
Pimenta, Renata
;
de Oliveira, Jose Salvador R.
;
Filho, Valdir C.
;
Macho, Antonio
;
Paredes-Gamero, Edgar J.
;
de Oliveira Martins, Domingos T.
Total Authors: 10
|
| Document type: | Journal article |
| Source: | BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS; v. 1861, n. 4, p. 958-967, APR 2017. |
| Web of Science Citations: | 9 |
| Abstract | |
Background: Canthin-6-one is a natural product isolated from various plant genera and from fungi with potential antitumor activity. In the present study, we evaluate the antitumor effects of canthin-6-one in human myeloid leukemia lineages. Methods: Kasumi-1 lineage was used as a model for acute myeloid leukemia. Cells were treated with canthin-6one and cell death, cell cycle and differentiation were evaluated in both total cells (Lin(+)) and leukemia stem cell population (CD34(+) CD38(-)Lin(-/low) Results: Among the human lineages tested, Kasumi-1 was the most sensitive to canthin-6-one. Canthin-6-one induced cell death with apoptotic (caspase activation, decrease of mitochondrial potential) and necrotic (lysosomal permeabilization, double labeling of annexin V/propidium iodide) characteristics. Moreover, canthin-6-one induced cell cycle arrest at Go/Gi (7 mu M) and G2 (45 mu m) evidenced by DNA content, BrdU incorporation and cyclin Bl/histone 3 quantification. Canthin-6-one also promoted differentiation of Kasumi-1, evidenced by an increase in the expression of myeloid markers (CD11 b and CD15) and the transcription factor PU.1. Furthermore, a reduction of the leukemic stem cell population and clonogenic capability of stem cells were observed. Conclusions: These results show that canthin-6-one can affect Kasumi-1 cells by promoting cell death, cell cycle arrest and cell differentiation depending on concentration used. General significance: Canthin-6-one presents an interesting cytotoxic activity against leukemic cells and represents a promising scaffold for the development of molecules for anti-leukemic applications, especially by its anti-leukemic stem cell activity. (C) 2017 Elsevier B.V. All rights reserved. (AU) | |
| FAPESP's process: | 15/16799-3 - Investigating the role of Intracellular Ca2+ as a modulator of leukemic and hematopoietic stem cells |
| Grantee: | Edgar Julian Paredes-Gamero |
| Support type: | Regular Research Grants |