Curcumin induces pro-apoptotic endoplasmic reticulum stress in human leukemia HL-60 cells
Curcumin induces pro-apoptotic endoplasmic reticulum stress in human leukemia HL-60 cells
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DOI：
10.1016/j.bbrc.2006.12.133
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发表时间：
2007-02-23
影响因子：
3.1
通讯作者：
Chung, Hun-Taeg
中科院分区：
文献类型：
--
作者：
Pae, Hyun-Ock;Jeong, Sun-Oh;Chung, Hun-Taeg
姜黄素已被证明可以诱导许多癌细胞凋亡。然而，姜黄素诱导细胞凋亡的分子机制尚不清楚，很可能涉及多种途径。在 HL-60 细胞中，姜黄素诱导细胞凋亡和内质网 (ER) 应激，这一点可以通过存活分子（如磷酸化蛋白激酶样 ER 驻留激酶、磷酸化真核起始因子 2 α、葡萄糖调节蛋白 78）以及凋亡分子（如 caspase-4 和 caspase-4）来证明。 CAAT/增强子结合蛋白同源蛋白（CHOP）。通过 z-LEVD-FMK 抑制 caspase-4 活性，通过小干扰 RNA 阻断 CHOP 表达，以及用 ER 抑制剂 salubrinal 治疗，可显着减少姜黄素诱导的细胞凋亡。姜黄素中的两个双键被认为与分泌蛋白中的硫醇形成迈克尔加合物，去除姜黄素中的两个双键会导致姜黄素诱导细胞凋亡和内质网应激的能力丧失。因此，本研究表明姜黄素诱导的细胞凋亡与其引起内质网应激的能力有关。 (c) 2006 Elsevier Inc. 保留所有权利。
Curcumin has been shown to induce apoptosis in many cancer cells. However, the molecular mechanism(s) responsible for curcumin-induced apoptosis is not well understood and most probably involves several pathways. In HL-60 cells, curcumin induced apoptosis and endoplasmic reticulum (ER) stress as evidenced by the survival molecules such as phosphorylated protein kinase-like ER-resident kinase, phosphorylated eukaryotic initiation factor-2 alpha, glucose-regulated protein-78, and the apoptotic molecules such as caspase-4 and CAAT/enhancer binding protein homologous protein (CHOP). Inhibition of caspase-4 activity by z-LEVD-FMK, blockage of CHOP expression by small interfering RNA, and treatment with salubrinal, an ER inhibitor, significantly reduced curcumin-induced apoptosis. Removing two double bonds in curcumin, which was speculated to form Michael adducts with thiols in secretory proteins, resulted in a loss of the ability of curcumin to induce apoptosis as well as ER stress. Thus, the present study shows that curcumin-induced apoptosis is associated with its ability to cause ER stress. (c) 2006 Elsevier Inc. All rights reserved.