Molecular mechanism of apoptosis induced by schizandrae-derived lignans in human leukemia HL-60 cells
Molecular mechanism of apoptosis induced by schizandrae-derived lignans in human leukemia HL-60 cells
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DOI：
10.1016/j.fct.2007.08.048
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发表时间：
2008-02-01
影响因子：
4.3
通讯作者：
Hou, De-Xing
中科院分区：
文献类型：
--
作者：
Lin, Shigang;Fujii, Makoto;Hou, De-Xing
五味子是一种传统的中草药，在中国医院临床上已被用于治疗B型肝炎。我们从S. chinensis。目前，我们报道了五味子甲素和五味子甲素γ可以诱导人早幼粒细胞白血病细胞（HL-60）发生凋亡，其特征是DNA断裂和聚（ADP）核糖聚合酶（PARP）切割。进一步的分子分析表明，脱氧野菊花苷和γ-野菊花苷引起线粒体膜电位（Δ Psim）的损失，细胞色素c从线粒体释放到胞质溶胶，Bid蛋白的截短，以及caspase-3和-9的激活。然而，它们并没有增加细胞内活性氧（ROS）的水平。抗氧化剂如N-乙酰半胱氨酸（NAC）和过氧化氢酶不能阻断脱氧野菊花苷或γ-野菊花苷诱导的细胞凋亡。这些结果表明，脱氧野百合素和γ-野百合素诱导HL-60细胞凋亡涉及ROS非依赖性线粒体功能障碍途径。(C)2007爱思唯尔有限公司保留所有权利。
Schizandrae chinensis, a traditional Chinese medicine herb, has been used to treat hepatitis B disease in Chinese hospital clinic. We have isolated two bioactive compounds, deoxyschizandrin and gamma-schizandrin, from S. chinensis. In the present, we reported that deoxyschizandrin and gamma-schizandrin could induce apoptosis in human promyelocytic leukemia cells (HL-60), as characterized by DNA fragmentation and poly (ADP) ribose polymerase (PARP) cleavage. Further molecular analysis showed that deoxyschizandrin and gamma-schizandrin caused the loss of mitochondrial membrane potential (Delta Psi m), cytochrome c release from mitochondrion to cytosol, truncation of Bid protein, and activation of caspase-3 and -9. However, they did not increase the intracellular level of reactive oxygen species (ROS). Antioxidants such as N-acetyl cysteine (NAC) and catalase did not block the apoptosis induced by deoxyschizandrin or,gamma-schizandrin. These findings suggest that deoxyschizandrin and gamma-schizandrin-induced apoptosis in HL-60 cells involved ROS-independent mitochondrial dysfunction pathway. (C) 2007 Elsevier Ltd. All rights reserved.