Canthin-6-one induces cell death, cell cycle arrest and differentiation in human myeloid leukemia cells

Autor(es)

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.

• Tipo de documento: Artigo Científico
• Fonte: BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS; v. 1861, n. 4, p. 958-967, APR 2017.
• Citações Web of Science: 9

Resumo

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)

• Processo FAPESP: 15/16799-3 - Investigação do papel do Ca2+ intracelular como modulador da célula-tronco hematopoética e leucêmica
• Beneficiário: Edgar Julian Paredes-Gamero
• Linha de fomento: Auxílio à Pesquisa - Regular