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

Abstract

Guohua Xia1,2, Baoan Chen1,2, Jiahua Ding1,2, Chong Gao1,2, Huixia Lu1,2, Zeye Shao1,2, Feng Gao1,2, Xuemei Wang2,31Department of Hematology, Zhongda Hospital, Medical School, Southeast University, Nanjing, People's Republic of China; 2Faculty of Oncology, Medical School, Southeast University, Nanjing, People’s Republic of China; 3National Key Laboratory of Bioelectronics (Chien-Shiung Wu Laboratory), Southeast University, Nanjing, People’s Republic of ChinaAbstract: 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