A new artemisinin derivative SM1044 induces apoptosis of Kasumi-1 cells and its mechanism / 中国实验血液学杂志

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.

Effect of arsenic trioxide on induction of apoptosis in MCL cell line and its possible mechanisms / 中国实验血液学杂志

This study was aimed to explore the effect of arsenic trioxide (ATO) on proliferation and apoptosis of mantle cell lymphoma (MCL) cell lines and the underlying mechanisms of the apoptosis. MCL cell lines (jeko-1, mino, JVM-2) were treated with different concentrations of ATO, then growth profile of these cells were detected by MTT. Apoptosis of ATO-treated jeko-1 cells were detected by flow cytometry with Annexin V-FITC/PI double staining. The loss of mitochondrial membrane potential of ATO-treated jeko-1 cells were detected by FCM with DiOC₆(3) staining. The expressions of cyclin D1 and apoptosis related proteins MCL-1, BCL-2, PUMA, NOXA, cCaspase-3 (cleaved caspase-3), cCaspase-9 (cleaved caspase-9), cPARP (cleaved PARP) were detected by Western blot. The results indicated that ATO inhibited cell growth, induced apoptosis of MCL cells and disrupted mitochondrial membrane potential. ATO could decrease expressions of MCL-1, PUMA and cyclin D1, increase expressions of cPARP, cCaspase-3, cCaspase-9 and the expressions of BLC-2 and NOXA were not changed. It is concluded that ATO can induce cell growth arrest and apoptosis of MCL cells. The mitochondrial pathway plays a very important role in cell apoptosis.