13,28-Epoxy triterpenoid saponins from Ardisia japonica selectively inhibit proliferation of liver cancer cells without affecting normal liver cells
13,28-Epoxy triterpenoid saponins from Ardisia japonica selectively inhibit proliferation of liver cancer cells without affecting normal liver cells
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紫金牛中的13,28-环氧三萜皂苷选择性抑制肝癌细胞增殖而不影响正常肝细胞
DOI：
10.1016/j.bmcl.2012.08.027
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发表时间：
2012-10-01
影响因子：
2.7
通讯作者：
Koike, Kazuo
中科院分区：
文献类型：
--
作者：
Li, Qin;Li, Wei;Koike, Kazuo
评价了来自紫金牛的20种13，28-环氧和相关三萜皂苷对人肝癌细胞和正常肝细胞的抗增殖活性。8种皂苷选择性地抑制肝癌细胞Bel-7402和HepG-2的生长，而不影响正常肝细胞HL-7702的存活。构效关系分析表明，皂苷元部分的13，28-环氧基、16 α-羟基和C-30甲基部分以及由四至七糖单元组成的糖基部分对该活性很重要。在活性皂苷中，紫金牛苷B（2）和3 β-O-β-D-吡喃葡萄糖基-（1 -> 2）-[α-L-吡喃鼠李糖基-（1 -> 2）-β-D-吡喃葡萄糖基-（1 -> 4）]-α-L-吡喃阿拉伯糖基-13 β，28-环氧-16 α-羟基齐墩果烷（3）对Bel-7402细胞显示出最有效的抗增殖活性，并呈剂量和时间依赖性。选择性抗增殖活性归因于肿瘤和正常肝细胞之间的不同细胞应答（CDKs和细胞周期蛋白水平、细胞周期阻滞和凋亡）。暴露于2和3选择性地导致Bel-7402细胞的细胞周期停滞和凋亡，以及促凋亡caspase-8的增加和抗凋亡Cdc 25 A的水平的降低。(C)2012爱思唯尔有限公司保留所有权利。
Twenty 13,28-epoxy and related triterpenoid saponins from Ardisia japonica were evaluated for their anti-proliferative activity on human liver cancer cells and normal liver cells. Eight saponins selectively inhibited the growth of liver cancer Bel-7402 and HepG-2 cells without affecting the survival of normal liver HL-7702 cells. The structure-activity relationship analyses indicated that the 13,28-epoxy, 16 alpha-hydroxy, and C-30 methyl moieties in the sapogenin parts and the glycosyl moiety consisting from tetrato hepta-saccharide units are important for this activity. Among the active saponins, ardisianoside B (2) and 3 beta-O-beta-D-glucopyranosyl-(1 -> 2)-[alpha-L-rhamnopyranosyl-(1 -> 2)-beta-D-glucopyranosyl-(1 -> 4)]-alpha-L-arabinopyranosyl-13 beta, 28-epoxy-16 alpha-hydroxyoleanane (3) showed the most potent anti-proliferative activity against Bel-7402 cells in a dose-and time-dependent manner. The selective anti-proliferative activity is attributed to the different cellular responses (CDKs and cyclins levels, cell cycle arrest and apoptosis) between tumor and normal liver cells. Exposure to 2 and 3 selectively led to cell cycle arrest and apoptosis in Bel-7402 cells together with the increased pro-apoptotic caspase-8 and the decreased anti-apoptotic Cdc25A levels. (C) 2012 Elsevier Ltd. All rights reserved.