title: 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.
authors.affiliation: Department of Hematology, Zhongda Hospital, Medical School, Southeast University, Nanjing, People's Republic of China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Xia
authors.forename: Baoan
authors.initials: B
authors.lastname: Chen
authors.forename: Jiahua
authors.initials: J
authors.lastname: Ding
authors.forename: Chong
authors.initials: C
authors.lastname: Gao
authors.forename: Huixia
authors.initials: H
authors.lastname: Lu
authors.forename: Zeye
authors.initials: Z
authors.lastname: Shao
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
mesh_terms: D000077584:2-Methoxyestradiol; D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000648:ultrastructure; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D050997:Nanomedicine; D010316:Particle Size
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; D004958:Estradiol; D000077584:2-Methoxyestradiol