Chair and Department of Microbiology and Immunology, Medical University of Silesia in Katowice, Jordana 19, 41-808 Zabrze, Poland.
Molecules. 2012 May 29;17(6):6449-64. doi: 10.3390/molecules17066449.
Coumarins are a very common type of secondary plant metabolites with a broad spectrum of biological activities. Psoralidin is a naturally occurring furanocoumarin isolated from Psoralea corylifolia possessing anticancer and chemopreventive properties. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cancer cells with no toxicity toward normal tissues. Endogenous TRAIL plays an important role in immune surveillance and defence against cancer cells. Coumarins can modulate TRAIL-mediated apoptosis in cancer cells. We examined the cytotoxic and apoptotic activities of psoralidin in combination with TRAIL on HeLa cancer cells. The cytotoxicity was measured by MTT and LDH assays. The apoptosis was detected using annexin V-FITC staining and mitochondrial membrane potential was evaluated using DePsipher staining by fluorescence microscopy. Death receptor (TRAIL-R1/DR4 and TRAIL-R2/DR5) expression was analyzed using flow cytometry. Psoralidin enhanced TRAIL-induced apoptosis in HeLa cells through increased expression of TRAIL-R2 death receptor and depolarization of mitochondrial membrane potential. Our study indicated that psoralidin augmented the anticancer effects of TRAIL and confirmed a potential use of coumarins in cancer chemoprevention.
香豆素是一种非常常见的次生植物代谢物，具有广泛的生物活性。补骨脂素是一种从补骨脂中分离出来的天然呋喃香豆素，具有抗癌和化学预防作用。肿瘤坏死因子相关凋亡诱导配体（TRAIL）在没有毒性的情况下诱导癌细胞凋亡，对正常组织没有毒性。内源性 TRAIL 在免疫监视和对抗癌细胞方面发挥着重要作用。香豆素可以调节 TRAIL 介导的癌细胞凋亡。我们研究了补骨脂素与 TRAIL 联合对 HeLa 癌细胞的细胞毒性和凋亡作用。细胞毒性通过 MTT 和 LDH 测定来衡量。通过流式细胞术分析凋亡，使用 annexin V-FITC 染色检测细胞凋亡，使用 DePsipher 染色通过荧光显微镜评估线粒体膜电位。用流式细胞术分析死亡受体（TRAIL-R1/DR4 和 TRAIL-R2/DR5）的表达。补骨脂素通过增加 TRAIL-R2 死亡受体的表达和线粒体膜电位去极化增强 TRAIL 诱导的 HeLa 细胞凋亡。我们的研究表明，补骨脂素增强了 TRAIL 的抗癌作用，并证实了香豆素在癌症化学预防中的潜在用途。
