| ChowJM |
------>authors3_c= ------>paper_class1=1 ------>Impact_Factor=3.408 ------>paper_class3=2 ------>paper_class2=1 ------>vol=36 ------>confirm_bywho=ncchang ------>insert_bywho=b681036 ------>Jurnal_Rank=21.1 ------>authors4_c= ------>comm_author= ------>patent_EDate=None ------>authors5_c= ------>publish_day=1 ------>paper_class2Letter=None ------>page2=148 ------>medlineContent= ------>unit=E0109 ------>insert_date=20080324 ------>iam=1 ------>update_date=None ------>author=??? ------>change_event=4 ------>ISSN=0301-472x ------>authors_c= ------>score=500 ------>journal_name=Experimental Hematology ------>paper_name=Downregulation of c-Myc determines sensitivity to 2-methoxyestradiol -induced apoptosis in human acute myeloid leukemia ------>confirm_date=20080326 ------>tch_id=089101 ------>pmid=18206725 ------>page1=140 ------>fullAbstract=OBJECTIVE: 2-Methoxyestradiol (2ME2) has been shown to induce apoptosis in leukemic cells, but its exact mechanism remains unclear. Because c-Myc plays a critical role in leukemogenesis, we evaluated whether 2ME2 acts on acute myeloid leukemia (AML) through modulation of c-Myc activity. MATERIALS AND METHODS: AML cell lines and primary AML leukemia were treated with 2ME2 and the relationship between 2ME2-induced apoptosis and changes in c-Myc activity was examined. RESULTS: 2ME2 induced mitochondrial apoptosis of human AML cells through increased reactive oxygen species. Further investigation showed that 2ME2 downregulated c-Myc expression in a time-dependent manner. Increased oxidative stress led to downregulation of c-Myc mRNA and protein, but did not affect the stability of c-Myc protein. To demonstrate the role of c-Myc in 2ME2-induced apoptosis, we ectopically expressed wild-type c-Myc in AML cells and found that ectopic expression of c-Myc abrogated the 2ME2-induced apoptosis. In addition, we showed that 2ME2 treatment inhibited phosphorylation of Akt and binding of nuclear factor-kappaB p65/p50 heterodimers to its DNA targets. As with results from cell lines studied, 2ME2 also induced cytotoxicity to primary AML cells and downregulated their c-Myc expression and induced apoptosis. CONCLUSION: Downregulation of c-Myc is critical for 2ME2-induced oxidative stress and apoptosis in AML cells. Our results might be extended to other types of cancers overexpressing c-Myc. ------>tmu_sno=None ------>sno=17150 ------>authors2=Liu CR ------>authors3=Lin CP ------>authors4=Lee CN ------>authors5=Cheng YC ------>authors6=Lin SF, Liu HE ------>authors6_c= ------>authors=ChowJM ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c= ------>publish_area=0 ------>updateTitle=Downregulation of c-Myc determines sensitivity to 2-methoxyestradiol-induced apoptosis in human acute myeloid leukemia. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no= ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2008 ------>submit_flag=None ------>publish_month=2 |