Polyphyllin D is a potent apoptosis inducer in drug-resistant HepG2 cells
Polyphyllin D is a potent apoptosis inducer in drug-resistant HepG2 cells
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DOI：
10.1016/j.canlet.2004.06.042
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发表时间：
2005-01-20
期刊：
影响因子：
9.7
通讯作者：
Kong, SK
中科院分区：
文献类型：
--
作者：
Cheung, JYN;Ong, RCY;Kong, SK
在寻找新的抗癌剂的过程中，我们鉴定了一种新型化合物polyphyllin D（PD）（薯蓣皂苷基α-L-吡喃鼠李糖基（1->2）-（α-L-阿拉伯呋喃糖基）-（1->4）]-[β-D-吡喃葡萄糖苷），其在具有耐药性的肝细胞癌细胞系HepG 2衍生物（R-HepG 2）中诱导DNA片段化和磷脂酰丝氨酸（PS）外化。PD是一种皂苷类化合物，最初发现于传统中药巴黎中。它在中国已被用于治疗肝癌多年。我们评估了该化合物在R-HepG 2及其亲本细胞中的细胞杀伤机制。线粒体凋亡途径被认为参与了PD诱导的细胞凋亡，因为PD引起的线粒体跨膜电位（DeltaPsim）的去极化，产生H2 O2，以及释放细胞色素c和凋亡诱导因子的剂量和时间依赖性的方式。总之，我们首次证明PD是一种有效的抗癌药物，可以克服R-HepG 2细胞的耐药性，并通过线粒体功能障碍引起细胞程序性死亡。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
In a search for new anticancer agents, we identified a novel compound polyphyllin D (PD) (diosgenyl alpha-L-rhamnopyranosyl(1-->2)-(alpha-L-arabinofuranosyl)-(1-->4)]-[beta-D-glucopyranoside) that induced DNA fragmentation and phosphatidyl-serine (PS) externalization in a hepatocellular carcinoma cell line HepG2 derivative with drug resistance (R-HepG2). PD is a saponin originally found in a tradition Chinese medicinal herb Paris polyphylla. It has been used to treat liver cancer in China for many years. We evaluated the cell-killing mechanisms of this compound in R-HepG2 and its parental cells. The mitochondrial apoptotic pathway was found to be involved in the PD-induced apoptosis because PD elicited depolarization of mitochondrial transmembrane potential (DeltaPsim), generation of H2O2, as well as release of cytochrome c and apoptosis-inducing factor in a dose- and time-dependent manner. In conclusion, we show for the first time that PD is a potent anticancer agent that can overcome drug resistance in R-HepG2 cells and elicit programmed cell death via mitochondrial dysfunction. (C) 2004 Elsevier Ireland Ltd. All rights reserved.