Induction of apoptosis by cordycepin via reactive oxygen species generation in human leukemia cells
Induction of apoptosis by cordycepin via reactive oxygen species generation in human leukemia cells
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DOI：
10.1016/j.tiv.2011.02.001
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发表时间：
2011-06-01
影响因子：
3.2
通讯作者：
Choi, Yung Hyun
中科院分区：
文献类型：
--
作者：
Jeong, Jin-Woo;Jin, Cheng-Yun;Choi, Yung Hyun
虫草素（Cordycepin，3 '-deoxyadenosin）是我国三大传统中药之一蛹虫草（Cordyceps militaris）的主要功能成分，是一种特异性的多聚腺苷酸化抑制剂。虫草素具有多种药理活性，包括免疫刺激、抗菌、抗病毒和抗肿瘤作用。然而，其抗癌机制的机制尚未被理解。本实验研究了虫草素对人白血病细胞的凋亡作用。虫草素治疗显着抑制细胞生长的浓度依赖性的方式诱导凋亡，但不坏死。这种诱导与活性氧（ROS）的产生，线粒体功能障碍，半胱天冬酶的激活，和聚（ADP-核糖）聚合酶蛋白的切割。然而，虫草素诱导的细胞凋亡被半胱天冬酶抑制剂减弱，表明半胱天冬酶在虫草素反应中的重要作用。给予ROS清除剂N-乙酰-L-半胱氨酸也能显著抑制虫草素诱导的细胞凋亡和半胱天冬酶的激活。这些结果支持了虫草素通过ROS介导的caspase通路的信号级联反应诱导人白血病细胞凋亡的机制。(C)2011爱思唯尔有限公司保留所有权利。
Cordycepin (3'-deoxyadenosin), a specific polyadenylation inhibitor, is the main functional component in Cordyceps militaris, one of the top three renowned traditional Chinese medicines. Cordycepin has been shown to possess many pharmacological activities including immunological stimulation, and anti-bacterial, anti-viral, and anti-tumor effects. However, the mechanisms underlying its anti-cancer mechanisms are not yet understood. In this study, the apoptotic effects of cordycepin were investigated in human leukemia cells. Treatment with cordycepin significantly inhibited cell growth in a concentration-dependent manner by inducing apoptosis but not necrosis. This induction was associated with generation of reactive oxygen species (ROS), mitochondrial dysfunction, activation of caspases, and cleavage of poly(ADP-ribose) polymerase protein. However, apoptosis induced by cordycepin was attenuated by caspase inhibitors, indicating an important role for caspases in cordycepin responses. Administration of N-acetyl-L-cysteine, a scavenger of ROS, also significantly inhibited cordycepin-induced apoptosis and activation of caspases. These results support a mechanism whereby cordycepin induces apoptosis of human leukemia cells through a signaling cascade involving a ROS-mediated caspase pathway. (C) 2011 Elsevier Ltd. All rights reserved.