Min Kyoung-Jin, Han Min Ae, Kim Shin, Park Jong-Wook, Kwon Taeg Kyu
Department of Immunology, School of Medicine, Keimyung University, Dalseo-Gu, Daegu 704-701, Republic of Korea.
Oncol Rep. 2017 Apr;37(4):2348-2354. doi: 10.3892/or.2017.5490. Epub 2017 Mar 6.
Osthole, an active constituent isolated from the fruit of Cnidium monnieri (L.) Cusson, has been shown to induce various beneficial biochemical effects such as anti-inflammatory and antitumor. In the present study, we examined whether osthole could sensitize TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human renal carcinoma Caki cells. We found that osthole and TRAIL alone, had no effect on apoptosis, but combined treatment with osthole and TRAIL markedly induced apoptosis in Caki (renal carcinoma), U251MG (glioma) and MDA-MB-231 (breast carcinoma) cells. In contrast, combined treatment with osthole and TRAIL did not induce apoptosis in normal human skin fibroblast cells. Osthole induced downregulation of cellular FLICE-like inhibitory protein (c-FLIP) expression, and overexpression of c-FLIP markedly blocked apoptosis induced by the combined treatment with osthole and TRAIL. In addition, osthole markedly reduced mitochondrial membrane potential levels, and increased cytosolic cytochrome c release in combined treatment with osthole and TRAIL. Therefore, these data suggest that osthole may be an efficient TRAIL sensitizer.
蛇床子素是从蛇床果实中分离得到的一种活性成分，已被证明具有多种有益的生化作用，如抗炎和抗肿瘤作用。在本研究中，我们检测了蛇床子素是否能增强肿瘤坏死因子相关凋亡诱导配体（TRAIL）诱导的人肾癌Caki细胞凋亡。我们发现，单独使用蛇床子素和TRAIL对细胞凋亡没有影响，但蛇床子素与TRAIL联合处理可显著诱导Caki（肾癌）、U251MG（胶质瘤）和MDA-MB-231（乳腺癌）细胞凋亡。相反，蛇床子素与TRAIL联合处理对正常人皮肤成纤维细胞没有诱导凋亡作用。蛇床子素可诱导细胞FLICE样抑制蛋白（c-FLIP）表达下调，而c-FLIP过表达可显著阻断蛇床子素与TRAIL联合处理诱导的细胞凋亡。此外，在蛇床子素与TRAIL联合处理时，蛇床子素可显著降低线粒体膜电位水平，并增加胞质细胞色素c的释放。因此，这些数据表明蛇床子素可能是一种有效的TRAIL增敏剂。
