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 Fe₃O₄ (MNPs-Fe₃O₄) on myelodysplastic syndrome (MDS) SKM-1 cells and its underlying mechanisms. The effect of the unique properties of tetraheptylammonium-capped MNPs-Fe₃O₄ 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-Fe₃O₄ 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-Fe₃O₄ carrier. Moreover, the copolymer of 2ME with MNPs- Fe₃O₄ blocked a nearly two-fold increase in SKM-1 cells located in G₂/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-Fe₃O₄ and control group. These findings suggest that the unique properties of MNPs-Fe₃O₄ 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.

Keywords:

• MDS
• MNPs-Fe₃O₄
• SKM-1 cell
• cell cycle

Acknowledgments

This work was financially supported by National Key Basic Research Program 973 of China (No. 2010CB732404), and National Science and Technology Support Program for the “Eleventh Five-Year” Plan (No. 2008BAI61B02).

Disclosure

The authors have no conflicts of interest to report in this work.