Mechanism of 2-methoxyestradiol-induced apoptosis in myelodysplastic syndrome MUTZ-1 cell line.

The study was aimed to investigate the mechanism of proliferation inhibition and apoptosis of MDS-RAEB MUTZ-1 cells induced by 2-methoxyestradiol (2-ME), the cell proliferation was determined by MTT assay, apoptosis rate was determined with annexinV-FITC/PI double staining and cell cycle was analyzed by flow cytometry (FCM) after MUTZ-1 cells were treated with different concentrations of 2-ME; the changes of morphologic features of MUTZ-1 cells were observed with Wright-Giemsa's staining; lactate dehydrogenase was determined by Beckman Counter; and agarose gel electrophoresis was used to verify whether 2-ME can induce apoptosis of MUTZ-1 cells. The results showed that 2-ME inhibited the proliferation of MUTZ-1 cells in a dose-and time-dependent manner and caused a sustained arrest at G(2)/M phase in MUTZ-1 cells; the typical apoptotic morphological features appeared in MUTZ-1 cells; the production of lactate dehydrogenase was up-regulated and the marked DNA ladder pattern of internucleosomal fragmentation was observed. It is concluded that the mechanism of proliferation inhibition and apoptosis of MUTZ-1 cells induced by 2-ME is probably related with the G(2)/M cell cycle arrest; 2-ME may be a potentially adjunctive anticancer drug useful to treat myelodysplastic syndrome.