Stobadine inhibits doxorubicin-induced apoptosis through a caspase-9 dependent pathway in P815 mastocytoma cells

Stobadine inhibits doxorubicin-induced apoptosis through a caspase-9 dependent pathway in P815 mastocytoma cells
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DOI:
10.1016/j.cellbi.2007.03.008
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发表时间:
2007-09-01
影响因子:
3.9
通讯作者:
Karasu, Cimen
Karasu, Cimen
中科院分区:
生物学4区
文献类型:
--
作者:
Bagriacik, E. Umit;Uslu, Kadriye;Karasu, Cimen

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多柔比星(DOXO)是一种广泛使用的化疗药物,可诱导转化和非转化细胞的凋亡。DOXO的凋亡作用与活性氧簇(ROS)的产生有关。抗氧化剂可有效地预防DOX诱导的细胞凋亡。在本研究中,我们研究的影响,stobadine,吡啶并吲哚类抗氧化剂在DOXO诱导的P815细胞凋亡模型的流式细胞仪分析和测量caspase-3和caspase-9的活性。用stobadine预处理细胞显著增加细胞活力和降低凋亡率。用10(-7)M司托巴定处理细胞后,观察到细胞凋亡抑制达到最大水平,这一点从流式细胞术分析中得到证实。通过抑制caspase-3和caspase-9的活性进一步证实了stobadine的抗凋亡作用。我们发现,司托巴定的抗氧化作用与众所周知的抗氧化剂N-乙酰L-半胱氨酸(NAC)的作用相当。(C)2007年国际细胞生物学联合会。由爱思唯尔有限公司出版。保留所有权利。
Doxorubicin (DOXO), a widely used chemotherapeutic agent, induces apoptosis in transformed and non-transformed cells. The apoptotic effect of DOXO has been linked to the generation of reactive oxygen species (ROS). Antioxidants may be effective in the prevention of DOX-induced apoptosis. In the present study we investigated the effects of stobadine, a pyridoindole antioxidant in a DOXO-induced apoptosis model of P815 cells by flow cytometric analyses and by measuring caspase-3 and caspase-9 activities. Pretreating cells with stobadine significantly increased cell viability and decreased apoptosis rate. Inhibition in apoptosis was observed at maximum levels following treatment of cells with 10(-7) M stobadine as evident from flow cytometric analyses. The antiapoptotic effect of stobadine was further confirmed by inhibition of caspase-3 and caspase-9 activities. We found that the antioxidative effects of stobadine were comparable to the effects of a well known antioxidant, N-acetyl L-cysteine (NAC). (C) 2007 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.