Effect of magnetic Fe3O4 nanoparticles with 2-methoxyestradiol on the cell-cycle progression and apoptosis of myelodysplastic syndrome cells.

Abstract

This study aims to evaluate the potential benefit of combination therapy of 2-methoxyestradiol (2ME) and magnetic nanoparticles of Fe(3)O(4) (MNPs-Fe(3)O(4)) on myelodysplastic syndrome (MDS) SKM-1 cells and its underlying mechanisms. The effect of the unique properties of tetraheptylammonium-capped MNPs-Fe(3)O(4) with 2ME on cytotoxicity was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell-cycle distribution and apoptosis were assessed by flow cytometry. The expression of cell-cycle marker protein was measured by Western blotting. Growth inhibition rate of SKM-1 cells treated with the 2ME-loaded MNPs-Fe(3)O(4) was enhanced when compared with 2ME alone. 2ME led to an increase of caspase-3 expression, followed by apoptosis, which was significantly increased when combined with an MNPs-Fe(3)O(4) carrier. Moreover, the copolymer of 2ME with MNPs- Fe(3)O(4) blocked a nearly two-fold increase in SKM-1 cells located in G(2)/M phase than in 2ME alone, which may be associated with an accompanying increase of p21 as well as a decrease in cyclin B1 and cdc2 expression, but there was no obvious difference between the MNPs-Fe(3)O(4) and control group. These findings suggest that the unique properties of MNPs-Fe(3)O(4) as a carrier for 2ME, a new anticancer agent currently in clinical trials, may be a logical strategy to enhance the therapeutic activity of MDS.