Canthin-6-one induces cell death, cell cycle arrest and differentiation in human myeloid leukemia cells
| Autor: | Roberto T. Araujo Júnior, Valdir Cechinel Filho, Renata Pimenta, Heron Fernandes Vieira Torquato, Antonio C. Ribeiro-Filho, Marcus V. Buri, Edgar J. Paredes-Gamero, Antonio Macho, Domingos Tabajara de Oliveira Martins, José Salvador Rodrigues de Oliveira |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cell cycle checkpoint Cellular differentiation Biophysics Apoptosis Biochemistry Indole Alkaloids 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Biomarkers Tumor Cytotoxic T cell Humans Cell Lineage Myeloid Cells Propidium iodide Molecular Biology Cell Death Chemistry Gene Expression Regulation Leukemic Myeloid leukemia Cell Differentiation Cell Cycle Checkpoints Cell cycle Leukemia Myeloid Acute 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Neoplastic Stem Cells Stem cell K562 Cells Leukemia inhibitory factor Carbolines |
| Zdroj: | Biochimica et biophysica acta. General subjects. 1861(4) |
| ISSN: | 0304-4165 |
| Popis: | 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-6-one 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 G0/G1 (7 μM) and G2 (45 μM) evidenced by DNA content, BrdU incorporation and cyclin B1/histone 3 quantification. Canthin-6-one also promoted differentiation of Kasumi-1, evidenced by an increase in the expression of myeloid markers (CD11b 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. |
| Databáze: | OpenAIRE |
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