[Regulation of 2-methoxyestradiol-induced cell apoptosis by mcl-1 and bax genes in myelodysplastic syndrome].
The purpose of this study was to explore the mechanism underlying the regulation of 2-methoxyestradiol (2-ME)-induced cell apoptosis by mcl-1 and bax gene in myelodysplastic syndrome (MDS). The MUTZ-1 cells were pretreated with 2-ME; then the activity of caspases-3 was determined by fluorescent colorimetry; the mRNA expressions of apoptosis-related genes (mcl-1) and bcl-2-related X protein (bax) were determined by RT-PCR. The results showed that as compared with control, the 2-ME enhanced the activity of caspase-3 in MUTZ-1 cells in a dose-and time-dependent manners (p<0.05); along with increasing of 2-ME concentration, the expression of intracellular mcl-1 mRNA reduced (p<0.05), meanwhile the expression level of mcl-1 mRNA negatively correlated to the activity of caspase-3 at the corresponding time points (r=-0.992, p<0.01), but the expression of bax mRNA did not show significant change (p>0.05). It is concluded that 2-ME can regulate the apoptosis of MDS cells through the pathway of down-regulating the expression of mcl-1 mRNA and activating the caspase-3.
Department of Hematology, Zhongda Hospital, Southeast University Clinical Medical College, Nanjing 210009, Jiangsu Province, China.
Guo-Hua
GH
Xia
Bao-An
BA
Chen
Hui-Xia
HX
Lu
Ze-Ye
ZY
Shao
Jia-Hua
JH
Ding
Chong
C
Gao
Ling-Li
LL
Hu
D000077584:2-Methoxyestradiol; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D004958:Estradiol / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000378:metabolism* / Q000473:pathology*; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
C494826:BAX protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D004958:Estradiol; D000077584:2-Methoxyestradiol; C505407:CASP3 protein, human; D053148:Caspase 3