Ellagic acid, a polyphenolic compound, selectively induces ROS-mediated apoptosis in cancerous B-lymphocytes of CLL patients by directly targeting mitochondria.
Ellagic acid, a polyphenolic compound, selectively induces ROS-mediated apoptosis in cancerous B-lymphocytes of CLL patients by directly targeting mitochondria.
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DOI：
10.1016/j.redox.2015.08.021
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发表时间：
2015-12
期刊：
影响因子：
11.4
通讯作者：
Pourahmad J
中科院分区：
文献类型：
--
作者：
Salimi A;Roudkenar MH;Sadeghi L;Mohseni A;Seydi E;Pirahmadi N;Pourahmad J
探讨黄花草酸（EA）对慢性淋巴细胞白血病（CLL）患者和健康人b淋巴细胞细胞毒性的影响。采用流式细胞术检测凋亡坏死率、细胞内活性氧自由基（ROS）、线粒体膜电位（MMP）和caspase-3活性，并从两组b淋巴细胞中分离线粒体，观察线粒体毒性参数。根据我们的结果，EA降低了活细胞百分比并诱导了细胞凋亡。EA增加了从CLL而非健康b淋巴细胞分离的线粒体中ROS形成、线粒体肿胀、MMP减少和细胞色素c释放，而环孢素A和丁基羟基甲苯（BHT）预处理可阻止这些作用。我们的研究结果表明，EA可以直接选择性靶向线粒体作为抗癌候选药物，通过线粒体途径诱导细胞凋亡，增加ROS的产生，最终导致细胞色素c释放、caspase 3激活和CLL患者癌性b淋巴细胞凋亡。EA直接选择性地靶向癌性b淋巴细胞中的线粒体。EA选择性地增加癌性b淋巴细胞的线粒体ROS。EA选择性地释放癌性b淋巴细胞中的线粒体细胞C。EA可通过线粒体途径选择性诱导细胞凋亡，作为CLL的抗癌候选药物。
To investigate the effects ofellagic acid (EA) on the cytotoxicity, B-lymphocytes isolated from CLL patients and healthy individuals. Flow cytometric assay was used to measure the percentage of apoptosis versus necrosis, intracellular active oxygen radicals (ROS), mitochondrial membrane potential (MMP) and the caspase-3 activity and then mitochondria were isolated from both groups B-lymphocytes and parameters of mitochondrial toxicity was investigated. Based on our results EA decreased the percentage of viable cells and induced apoptosis. EA increased ROS formation, mitochondria swelling, MMP decrease and cytochrome c release in mitochondria isolated from CLL BUT NOT healthy B-lymphocytes while pre-treatment with cyclosporine A and Butylated hydroxyl toluene (BHT) prevented these effects. Our results suggest that EA can act as an anti cancer candidate by directly and selectively targeting mitochondria could induce apoptosis through mitochondria pathway with increasing ROS production which finally ends in cytochrome c release, caspase 3 activation and apoptosis in cancerous B-lymphocytes isolated from CLL patients. EA directly and selectively targets mitochondria in cancerous B-lymphocytes. EA selectively increases mitochondrial ROS in cancerous B-lymphocytes. EA selectively releases mitochondrial cyt C in cancerous B-lymphocytes. EA can act as an anti-cancer candidate in CLL by selectively inducing apoptosis through mitochondrial pathway.