title: [A new artemisinin derivative SM1044 induces apoptosis of Kasumi-1 cells and its mechanism].
abstract: The aim of this study was to investigate the apoptosis-inducing effect of artemisinin derivative SM1044 on Kasumi-1 cells and its possible mechanism. Kasumi-1 cells were treated with different concentrations of SM1044, the cell viability was evaluated by MTT assay. Cell apoptosis and cell cycle progression were assessed by using flow cytometry with Annexin-V/PI double staining and flow cytometry with PI staining respectively. The expression of apoptosis-related proteins caspase 3, PARP and the fusion protein AML1-ETO were detected by Western blot. The results indicated that SM1044 inhibited cell growth of Kasumi-1 cells in time- and dose-dependent manners. After exposure of Kasumi-1 cells to 1 µmol/L SM1044 for 24 hours, the cell viability was decreased to 50%. IC(50) of SM1044 to Kasumi-1 cells at 48 hours was 0.17 ± 0.067 µmol/L. SM1044 induced cell apoptosis in a caspase-dependent manner, and the apoptotic rate of Kasumi-1 cells increased as SM1044 concentration increased. Flow cytometry with PI staining revealed that SM1044 induced cell cycle arrest, and the proportion of cells in G(0)/G(1) phase increased from 58.33 ± 4.46% to 71.75 ± 2.24% after exposure to 5 µmol/L SM1044 for 24 hours. Western blot showed that SM1044 increased the expression of apoptosis-related proteins cPARP and cleaved caspase 3 and also degraded the AML1-ETO fusion protein. It is concluded that SM1044 can inhibit the proliferation of Kasumi-1 cells, induce cell apoptosis which may be related to the increased level of cleaved PARP and cleaved caspase 3. SM1044 can also induce cell arrest in G(0)/G(1) phase. As the fusion protein AML1-ETO degrades obviously, it can be the potential target of SM1044 in Kasumi-1 cells.
authors: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Department of Hematology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
authors: Jing-Jing
authors: JJ
authors: Liu
authors: Ai-Mei
authors: AM
authors: Fei
authors: Rui-Min
authors: RM
authors: Nie
authors: Jin
authors: J
authors: Wang
authors: Ying
authors: Y
authors: Li
authors: Zhen-Yi
authors: ZY
authors: Wang
authors: Jian-Qing
authors: JQ
authors: Mi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D037621:Artemisinins / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; D037621:Artemisinins; C569247:SM1044