Downregulation of c-Myc determines the sensitivity to 2-methoxyestradiol-induced apoptosis in acute myeloid leukemia
| العنوان: | Downregulation of c-Myc determines the sensitivity to 2-methoxyestradiol-induced apoptosis in acute myeloid leukemia |
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| المؤلفون: | 劉興璟, Jyh-Ming Chow, Chien-Ru Liu, Che-Pin Lin, Chun-Nin Lee, Yun-Chih Cheng, Shufan Lin, H. Eugene Liu |
| المساهمون: | 臨床醫學研究所 |
| سنة النشر: | 2008 |
| المجموعة: | Taipei Medical University Repository (TMUR) |
| الوصف: | 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. |
| نوع الوثيقة: | other/unknown material |
| اللغة: | English |
| Relation: | xperimental Hematology.(36):140-148.; http://libir.tmu.edu.tw/handle/987654321/3105; http://libir.tmu.edu.tw/bitstream/987654321/3105/1/全文.txt; http://libir.tmu.edu.tw/bitstream/987654321/3105/2/摘要.pdf |
| الاتاحة: | http://libir.tmu.edu.tw/handle/987654321/3105 http://libir.tmu.edu.tw/bitstream/987654321/3105/1/全文.txt http://libir.tmu.edu.tw/bitstream/987654321/3105/2/摘要.pdf |
| رقم الانضمام: | edsbas.8BC5274F |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |