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.
Xia
Guo-Hua
GH
Department of Hematology, The Affiliated Zhongda Hospital, Clinical Medical College of Southeast University, Nanjing 210009, China.
Chen
Bao-An
BA
Shao
Ze-Ye
ZY
Lu
Hui-Xia
HX
Konstanze
Döhner
D
Hartmut
Döhner
D
D000077584:2-Methoxyestradiol; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009190:Myelodysplastic Syndromes / Q000473:pathology*
D000970:Antineoplastic Agents; D004958:Estradiol; D000077584:2-Methoxyestradiol; D007770:L-Lactate Dehydrogenase