| Autor: |
Shirato K; Laboratory of Physiological Sciences, Faculty of Human Sciences, Waseda University, Tokorozawa, Saitama 359-1192, Japan., Imaizumi K, Miyazawa K, Takasaki A, Mizuguchi J, Che XF, Akiyama S, Tomoda A |
| Jazyk: |
angličtina |
| Zdroj: |
Biological & pharmaceutical bulletin [Biol Pharm Bull] 2008 Jan; Vol. 31 (1), pp. 62-7. |
| DOI: |
10.1248/bpb.31.62 |
| Abstrakt: |
The aim of the present study was to investigate the mechanism of apoptosis in human multiple myeloma cell line, U266, caused by 2-aminophenoxazine-3-one (Phx-3). Flow-cytometrical and morphological analyses showed that Phx-3 increased the population of annexin V-positive cells including early stage apoptotic cells and late stage apoptotic cells and induced DNA fragmentation or apoptotic body formation in U266 cells, indicating that Phx-3 induced the apoptosis of U266 cells. Activity of caspase-3 was extensively increased in U266 cells treated with Phx-3 time-dependently within 24 h, but this Phx-3-stimulated activity of the enzyme in the cells was completely cancelled by the addition of N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk), a pan-caspase inhibitor. The addition of z-VAD-fmk almost blocked the apoptotic effect of Phx-3 against U266 cells, indicating that Phx-3-induced apoptosis of U266 cells was dependent on a caspase signaling pathway. Moreover, the apoptosis of U266 cells occurred after the induction of cell cycle arrest of the cells in the S and G(2)/M phase, the loss of mitochondrial membrane potential, and activation of caspase-3 reached maximum, which were caused by Phx-3 within 24 h. These results support the views that the apoptosis of U266 cells caused by Phx-3 may be preceded by the cell cycle arrest, depolarization of mitochondria and activation of caspase-3. These results support the view that Phx-3 may be utilized in future as chemotherapeutic agent against multiple myeloma which is extremely refractory to chemotherapy. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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