Ginseng saponin metabolite 20(S)-protopanaxadiol inhibits tumor growth by targeting multiple cancer signaling pathways.
Ginseng saponin metabolite 20(S)-protopanaxadiol inhibits tumor growth by targeting multiple cancer signaling pathways.
复制标题
人参皂苷代谢物 20(S)-原人参二醇通过靶向多个癌症信号通路抑制肿瘤生长
DOI：
10.3892/or.2013.2438
复制
发表时间：
2013-07
期刊：
影响因子：
4.2
通讯作者：
He TC
中科院分区：
文献类型：
--
作者：
Gao JL;Lv GY;He BC;Zhang BQ;Zhang H;Wang N;Wang CZ;Du W;Yuan CS;He TC
植物源性活性成分及其半合成或合成类似物已成为抗癌药物的主要来源。20（S）-原人参二醇（PPD）是西洋参（Panax quinquefolius L.）和亚洲人参（Panax ginseng C.A.）Meyer）。我们先前证明了PPD的葡萄糖苷前体Rg 3在异种移植模型中对HCT 116细胞表现出抗增殖作用并减小肿瘤大小。我们随后的研究表明，PPD具有更强的体外抗肿瘤活性比Rg 3，虽然PPD的抗癌活性的机制仍有待确定。在这里，我们研究了PPD在体外和体内人癌细胞中的抗癌活性的机制。PPD显示抑制HCT 116细胞的生长并诱导细胞周期停滞。体内研究表明，PPD可抑制携带HCT 116细胞的无胸腺裸鼠的异种移植瘤生长。当用PPD（30 mg/kg体重）处理动物3周时，异种移植肿瘤尺寸显著减小。当分析先前鉴定的Rg 3靶点A激酶（PRKA）锚蛋白8（AKAP 8L）和磷脂酰肌醇转移蛋白α（PITPNA）的表达时，显示PPD抑制PITPNA的表达，同时上调HCT 116细胞中AKAP 8L的表达。通路特异性报告基因检测结果表明，PPD能有效抑制NF-κB、JNK和MAPK/ERK信号通路。综上所述，我们的结果表明，PPD在结肠癌细胞中的抗癌活性可能是通过靶向NF-κB，JNK和MAPK/ERK信号通路介导的，尽管PPD作用的抗癌模式的详细机制需要充分阐明。
Plant-derived active constituents and their semi-synthetic or synthetic analogs have served as major sources of anticancer drugs. 20(S)-protopanaxadiol (PPD) is a metabolite of ginseng saponin of both American ginseng (Panax quinquefolius L.) and Asian ginseng (Panax ginseng C.A. Meyer). We previously demonstrated that ginsenoside Rg3, a glucoside precursor of PPD, exhibits anti-proliferative effects on HCT116 cells and reduces tumor size in a xenograft model. Our subsequent study indicated that PPD has more potent antitumor activity than that of Rg3 in vitro although the mechanism underlying the anticancer activity of PPD remains to be defined. Here, we investigated the mechanism underlying the anticancer activity of PPD in human cancer cells in vitro and in vivo. PPD was shown to inhibit growth and induce cell cycle arrest in HCT116 cells. The in vivo studies indicate that PPD inhibits xenograft tumor growth in athymic nude mice bearing HCT116 cells. The xenograft tumor size was significantly reduced when the animals were treated with PPD (30 mg/kg body weight) for 3 weeks. When the expression of previously identified Rg3 targets, A kinase (PRKA) anchor protein 8 (AKAP8L) and phosphatidylinositol transfer protein α (PITPNA), was analyzed, PPD was shown to inhibit the expression of PITPNA while upregulating AKAP8L expression in HCT116 cells. Pathway-specific reporter assays indicated that PPD effectively suppressed the NF-κB, JNK and MAPK/ERK signaling pathways. Taken together, our results suggest that the anticancer activity of PPD in colon cancer cells may be mediated through targeting NF-κB, JNK and MAPK/ERK signaling pathways, although the detailed mechanisms underlying the anticancer mode of PPD action need to be fully elucidated.
登录
查看更多内容
复合K是人参皂苷的代谢产物，通过HL-60人白血病细胞中的caspase-8依赖性途径诱导凋亡。
影响因子：
3.8
作者：
Cho SH;Chung KS;Choi JH;Kim DH;Lee KT
通讯作者：
Lee KT
影响因子：
6.4
作者：
Jung, SH;Woo, MS;Kim, HS
通讯作者：
Kim, HS
影响因子：
5
作者：
Kim, Sun Mi;Lee, So Yong;Hong, Jin Tae
通讯作者：
Hong, Jin Tae
DOI：
10.1111/j.1742-7843.2006.pto_415.x
发表时间：
2006-06-01
影响因子：
3.1
作者：
Li, Gang;Wang, Zhenhua;Wang, Ziren
通讯作者：
Wang, Ziren
DOI：
10.5560/znc.2011.66c0199
发表时间：
2011-05-01
影响因子：
2
作者：
Li, Ning;Huang, Yuan;Li, Pingya
通讯作者：
Li, Pingya