Involvement of reactive oxygen species, but not mitochondrial permeability transition in the apoptotic induction of human SK-Hep-1 hepatoma cells by shikonin
Involvement of reactive oxygen species, but not mitochondrial permeability transition in the apoptotic induction of human SK-Hep-1 hepatoma cells by shikonin
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DOI：
10.1055/s-2003-45193
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发表时间：
2003-12-01
期刊：
影响因子：
2.7
通讯作者：
Liu, TZ
中科院分区：
文献类型：
--
作者：
Chen, CH;Chern, CL;Liu, TZ
紫草素已被证明具有抗癌活性，但其潜在机制尚不清楚。在本报告中，我们发现紫草素的管理可以导致诱导人肝癌细胞株SK-Hep-1的细胞凋亡。如流式细胞术研究所证实的，紫草素具有在该凋亡过程的早期阶段产生增加量的细胞内活性氧物质（ROS）的能力（约200 mg/ml）。1小时），随后在3小时时伴随线粒体跨膜电位（Δ Psi（m））的消散。进一步的研究表明，用谷胱甘肽（GSH）和N-乙酰半胱氨酸（NAC）预处理紫草素处理的细胞，可以有效地保护这种凋亡过程，但不能被线粒体通透性转换（NIPT）孔抑制剂环孢菌素A（CyA）所保护。这些数据进一步证明ROS介导的氧化应激是参与诱导SK-Hep-1细胞凋亡的关键因素。综上所述，我们认为紫草素诱导的SK-Hep-1细胞凋亡是通过氧化应激介导的途径进行的。
Shikonin has been demonstrated to exhibit anti-cancer activity, but the underlying mechanisms are poorly understood. In this report, we showed that the administration of shikonin could result in the induction of apoptotic cell death of human hepatoma cell line, SK-Hep-1. As evident by the flow-cytometric studies, shikonin has the capability of generating increased amounts of intracellular reactive oxygen species (ROS) during the early stage of this apoptotic process (ca. one-hour), and subsequently accompanied by the dissipation of mitochondrial transmembrane potential (DeltaPsi(m)) at 3 hours. Further studies indicated that this apoptotic process could effectively be protected by the pretreatment of shikonin-treated cells with glutathione (GSH) and Nacetylcysteine (NAC), a precursor of GSH, but not by cyclosporin A (CyA), an inhibitor of mitochondrial permeability transition (NIPT) pore. These data further proved that ROS-mediated oxidative stress was the pivotal element involved in the induction of apoptosis of SK-Hep-1 cells. Taken together, we suggest that shikonin-induced apoptosis of SK-Hep-1 cells proceeds by an oxidative stress-mediated pathway.