Kim Areum Daseul, Madduma Hewage Susara Ruwan Kumara, Piao Mei Jing, Kang Kyoung Ah, Cho Suk Ju, Hyun Jin Won
School of Medicine, Jeju National University, Jeju, Korea.
Cell Biochem Funct. 2015 Oct;33(7):487-94. doi: 10.1002/cbf.3146. Epub 2015 Oct 5.
Colorectal cancer has become more common in many regions of the world. Recently, we showed that esculetin, a natural coumarin, induces apoptosis in HT-29 colon cancer cells via the reactive oxygen species-mediated mitochondrial pathway. The present study examined whether esculetin induces apoptosis in HT-29 colon cancer cells by inducing endoplasmic reticulum (ER) stress. We found that esculetin induced characteristic signs of ER stress, confirmed by ER staining, mitochondrial calcium overload and expression of ER stress-related proteins (i.e. glucose regulated protein 78, phosphorylated ribonucleic acid-dependent protein kinase-like ER kinase, phosphorylated inositol requiring enzyme 1, phosphorylated eukaryotic initiation factor-2α, spliced X-box binding protein 1 and cleaved activating transcription factor 6). Esculetin also induced the expression of the CCAAT/enhancer-binding protein-homologous protein (CHOP) and pro-apoptotic factors caspase-12. Moreover, transfection of colon cancer cells with a small interfering ribonucleic acid targeting CHOP attenuated esculetin-induced apoptosis. Taken together, these results suggest that the ER stress response plays an important role in esculetin-induced apoptosis in human colon cancer cells.
在世界许多地区，结直肠癌已变得愈发常见。最近，我们发现七叶亭（一种天然香豆素）通过活性氧介导的线粒体途径诱导HT - 29结肠癌细胞凋亡。本研究探讨了七叶亭是否通过诱导内质网（ER）应激来诱导HT - 29结肠癌细胞凋亡。我们发现七叶亭诱导了ER应激的特征性迹象，这通过ER染色、线粒体钙超载以及ER应激相关蛋白（即葡萄糖调节蛋白78、磷酸化的依赖核糖核酸的蛋白激酶样ER激酶、磷酸化的肌醇需求酶1、磷酸化的真核起始因子 - 2α、剪接的X盒结合蛋白1和裂解的活化转录因子6）的表达得以证实。七叶亭还诱导了CCAAT/增强子结合蛋白同源蛋白（CHOP）和促凋亡因子半胱天冬酶 - 12的表达。此外，用靶向CHOP的小干扰核糖核酸转染结肠癌细胞可减弱七叶亭诱导的凋亡。综上所述，这些结果表明ER应激反应在七叶亭诱导人结肠癌细胞凋亡中起重要作用。
