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

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.

Influence of protein corona on the transport of molecules into cells by mesoporous silica nanoparticles.

Although there are several studies reporting the promising biological efficiency of mesoporous silica nanoparticles (loaded with antitumoral drugs) against cancer cells and tumors, there are no reports on the influence of the bio-nano interface interactions on the molecular diffusion process occurring along their pores. In this context, we show here that the protein coating formed on multifunctionalized colloidal mesoporous silica nanoparticles (MSNs) dispersed in a cell culture medium decreases the release of camptothecin (CPT, a hydrophobic antitumoral drug) from the pores of MSNs. This effect is related to the adsorption of biomolecules on the nanoparticle surface, which partially blocks the pores. Parallely, the hydrophobic functionalization inside the pores can offer suitable sites for the adsorption of other molecules present in the cell culture medium depending on the hydrophobicity, size, and conformation aspects of these molecules and adsorption sites of MSNs. Thus, the molecular cargo loaded in the pores (i.e. CPT) can be replaced by specific molecules present in the dispersion medium. As a consequence, we show that a non-permeable cellular staining molecule such as SYTOX green can be incorporated in MSNs through this mechanism and internalized by cells in an artificial fashion. By extrapolating this phenomenon for applications in vivo, one has to consider now the possible manifestation of unpredicted biological effects from the use of porous silica nanoparticles and others with similar structure due to these internalization aspects.