Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, South Korea.
Basic Clin Pharmacol Toxicol. 2011 Oct;109(4):283-91. doi: 10.1111/j.1742-7843.2011.00717.x. Epub 2011 May 31.
To assess the ability of 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1) to promote apoptosis, we investigated the effect of YC-1 on tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in the human epithelial ovarian carcinoma cell lines. In OVCAR-3 and SK-OV-3 cell lines, we examined the stimulatory effect of YC-1 on TRAIL-induced apoptosis by monitoring cell death, nuclear damage, changes in apoptosis-related protein levels, activation of caspases and changes in the mitochondrial transmembrane potential. TRAIL induced a decrease in Bid, Bcl-2 and Bcl-xL protein levels, increase in cleaved Bid and Bax levels, loss of the mitochondrial transmembrane potential, cytochrome c release, activation of caspases (-8, -9 and -3) and an increase in the tumour suppressor p53 levels. YC-1 enhanced TRAIL-induced apoptosis-related protein activation, nuclear damage and cell death. Results from this study suggest that YC-1 may enhance the apoptotic effect of TRAIL on ovarian carcinoma cell lines by increasing the activation of the caspase-8- and Bid-dependent pathways and the mitochondria-mediated apoptotic pathway, leading to caspase activation. YC-1 may confer a benefit in TRAIL treatment of epithelial ovarian adenocarcinoma.
为了评估 3-(5'-羟甲基-2'-呋喃基)-1-苯甲基吲唑（YC-1）促进细胞凋亡的能力，我们研究了 YC-1 对肿瘤坏死因子（TNF）相关凋亡诱导配体（TRAIL）诱导的人上皮性卵巢癌细胞系凋亡的影响。在 OVCAR-3 和 SK-OV-3 细胞系中，我们通过监测细胞死亡、核损伤、凋亡相关蛋白水平变化、半胱天冬酶激活和线粒体跨膜电位变化，检测了 YC-1 对 TRAIL 诱导凋亡的刺激作用。TRAIL 诱导 Bid、Bcl-2 和 Bcl-xL 蛋白水平降低，裂解 Bid 和 Bax 水平升高，线粒体跨膜电位丧失，细胞色素 c 释放，半胱天冬酶（-8、-9 和 -3）激活和肿瘤抑制因子 p53 水平升高。YC-1 增强了 TRAIL 诱导的凋亡相关蛋白激活、核损伤和细胞死亡。本研究结果表明，YC-1 可能通过增加半胱天冬酶-8 和 Bid 依赖性途径以及线粒体介导的凋亡途径的激活，增强 TRAIL 对卵巢癌细胞系的凋亡作用，从而导致半胱天冬酶激活。YC-1 可能有助于 TRAIL 治疗上皮性卵巢腺癌。
