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Canthin-6-one induces cell death, cell cycle arrest and differentiation in human myeloid leukemia cells
Heron F Vieira Torquato1, Antonio C Ribeiro-Filho2, Marcus V Buri3
1Department of Basic Sciences in Health, Faculty of Medicine, Federal University of Mato Grosso (UFMT), Av. Fernando Correa da Costa, no. 2367, Boa Esperança, Cuiabá, Mato Grosso 78060-900, Brazil; Department of Biochemistry, Federal University of São Paulo (UNIFESP), Av. Pedro de Toledo, no. 669, São Paulo, São Paulo 04039-401, Brazil.
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 (7μM) and G2 (45μM) 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.
Insights
Canthin-6-one, a natural product, effectively combats human myeloid leukemia cells by inducing cell death, halting cell cycle progression, and promoting differentiation. It also targets and reduces the leukemic stem cell population.
Area of Science:
- Natural product chemistry
- Cancer biology
- Hematology
Background:
- Canthin-6-one is a natural product with documented antitumor potential.
- This study investigates its efficacy against human myeloid leukemia cell lines.
Purpose of the Study:
- To evaluate the antitumor effects of canthin-6-one on human myeloid leukemia lineages.
- To assess its impact on cell death, cell cycle, and differentiation.
Main Methods:
- Kasumi-1 cells, a model for acute myeloid leukemia, were treated with canthin-6-one.
- Evaluations included cell death, cell cycle, and differentiation markers in both total and stem cell populations.
Main Results:
- Canthin-6-one induced both apoptotic and necrotic cell death in Kasumi-1 cells.
- It caused cell cycle arrest at G0/G1 and G2 phases and promoted myeloid differentiation.
- A significant reduction in leukemic stem cell population and clonogenic capacity was observed.
Conclusions:
- Canthin-6-one demonstrates concentration-dependent effects on leukemia cells, including cell death, cycle arrest, and differentiation.
- It exhibits promising cytotoxic activity against leukemic cells, particularly targeting leukemia stem cells.
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