Potent proapoptotic actions of dihydroartemisinin in gemcitabine-resistant A549 cells.
Potent proapoptotic actions of dihydroartemisinin in gemcitabine-resistant A549 cells.
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双氢青蒿素对吉西他滨耐药的 A549 细胞具有有效的促凋亡作用。
DOI：
10.1016/j.cellsig.2014.07.001
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发表时间：
2014-10
期刊：
影响因子：
--
通讯作者：
Tongsheng Chen
中科院分区：
文献类型：
--
作者：
Gaina xi;Tan Li;Shengnan Wu;Tongsheng Chen
我们最近的研究表明，活性氧（ROS）介导的caspase-8和caspase-8依赖的凋亡途径在双氢青蒿素（DHA）诱导的A549细胞凋亡中起着关键作用。本研究旨在探讨DHA在吉西他滨耐药A549（A549 GR）细胞中的促凋亡机制。A549 GR细胞的基础抗氧化能力低于GEM敏感的A549（A549）细胞，而基础ROS水平和细胞内Fe ~（2+）水平高于GEM敏感的A549（A549）细胞。与Gem诱导的缓慢ROS生成相反，DHA在30分钟内诱导快速ROS生成。此外，Gem在两种细胞系中诱导相似的ROS产生，而DHA在A549 GR细胞中诱导的ROS产生多于A549细胞。更重要的是，DHA处理后，A549 GR细胞表现出比A549细胞更强的Bax激活、线粒体膜电位（Δ Δ Km）损失、caspase激活和凋亡诱导。此外，NAC预处理有效地阻止了DHA诱导的ROS产生和Δ m的丢失以及凋亡，并且通过shRNA沉默Bax或抑制caspase-3、-8和-9中的一种也显著地阻止了两种细胞系中DHA诱导的凋亡，这表明ROS和Bax以及caspase的关键作用。总的来说，DHA通过ROS依赖的凋亡途径在A549 GR细胞中比在正常A549细胞中呈现更强的促凋亡作用，其中涉及Bax和caspase。
Our recent studies have demonstrated the key roles of reactive oxygen species (ROS)-mediated caspase-8- and Bax-dependent apoptotic pathways in dihydroartemisinin (DHA)-induced apoptosis of A549 cells. This report is designed to investigate the proapoptotic mechanisms of DHA in gemcitabine (Gem)-resistant A549 (A549GR) cells. A549GR cells exhibited lower basal antioxidant capacity, higher level of basal ROS and intracellular Fe2 +than Gem-sensitive A549 (A549) cells. In contrast to the sluggish ROS generation induced by Gem, DHA induced a rapid ROS generation within 30 min. Moreover, Gem induced similar ROS generation in both cell lines, while DHA induced more ROS generation in A549GR cells than in A549 cells. More importantly, after treatment with DHA, A549GR cells showed more potent induction in Bax activation, loss of mitochondrial membrane potential (ΔΨm), caspase activation and apoptosis than A549 cells. Furthermore, NAC pretreatment potently prevented DHA-induced ROS generation and loss of ΔΨm as well as apoptosis, and silencing Bax by shRNA or inhibition of one of caspase-3, -8 and -9 also significantly prevented DHA-induced apoptosis in both cell lines, indicating the key roles of ROS and Bax as well as the caspases. Collectively, DHA presents more potent proapoptotic actions in A549GR cells preferentially over normal A549 cells via ROS-dependent apoptotic pathway, in which Bax and caspases are involved.
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影响因子：
4.8
作者：
Wei-wei Zhang;Xiaopin Wang;Tongsheng Chen
通讯作者：
Wei-wei Zhang;Xiaopin Wang;Tongsheng Chen
双氢青蒿素耐药结肠癌HCT116/R细胞系的表征
影响因子：
4.3
作者：
Lu, Jin-Jian;Chen, Si-Meng;Ding, Jian;Meng, Ling-Hua
通讯作者：
Meng, Ling-Hua
影响因子：
3.5
作者：
Lu, Ying-Ying;Chen, Tong-Sheng;Chen, Min
通讯作者：
Chen, Min
影响因子：
9.7
作者：
Wang, Shuang-Jia;Gao, Yue;Sun, Bei
通讯作者：
Sun, Bei
DOI：
10.1016/j.tiv.2011.10.004
发表时间：
2012-02
期刊：
Toxicology in vitro : an international journal published in association with BIBRA
影响因子：
--
作者：
Jingyun Wang;Pingping Sun;Y. Bao;Bairui Dou;Dandan Song;Yachen Li
通讯作者：
Jingyun Wang;Pingping Sun;Y. Bao;Bairui Dou;Dandan Song;Yachen Li