A novel component from citrus, ginger, and mushroom family exhibits antitumor activity on human meningioma cells through suppressing the Wnt/β-catenin signaling pathway.
A novel component from citrus, ginger, and mushroom family exhibits antitumor activity on human meningioma cells through suppressing the Wnt/β-catenin signaling pathway.
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DOI：
10.1007/s13277-015-3388-0
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发表时间：
2015-09
期刊：
影响因子：
--
通讯作者：
Patel, Sunil J.
中科院分区：
文献类型：
--
作者：
Das, Arabinda;Miller, Rickey;Lee, Philip;Holden, Chrysanthe Alyssa;Lindhorst, Scott M.;Jaboin, Jerry;Vandergrift, William A., III;Banik, Naren L.;Giglio, Pierre;Varma, Abhay K.;Raizer, Jeffery J.;Patel, Sunil J.
复发性脑膜瘤是一个罕见的，但重要的问题后，标准（手术和放射）治疗失败。目前的化疗（羟基脲，RU-486和干扰素-α）只有边际效益。对于手术和放射治疗失败的脑膜瘤患者，迫切需要更有效的治疗方法。柠檬苦素、橘子素、泽尔金、6-姜酚、灵芝酸A和灵芝酸DM是一些具有抗肿瘤特性并在体外引起脑膜瘤细胞死亡的植物衍生物。由于其易于管理，长期耐受性和长期副作用的发生率低，我们通过检查其体外对脑膜瘤细胞的疗效来探索其作为脑膜瘤治疗剂的潜力。采用MTT法、Western印迹法、半胱天冬酶法和DNA片段化法评价治疗效果。结果表明，用柠檬苦素、橘子素、泽尔丁、6-姜酚、灵芝酸A和灵芝酸DM处理IOMM-Lee和CH 157 MN脑膜瘤细胞诱导凋亡，并通过抑制Wnt 5/β-连环蛋白途径增强糖原合成酶激酶3 β（GSK 3 β）的磷酸化。这些药物在正常人神经元中不诱导凋亡。细胞凋亡中的其他事件包括四跨膜蛋白（TSPAN 12）、存活蛋白（Bcl-XL和Mcl-1）的下调以及凋亡因子（Bax和caspase-3）的过表达。这些结果提供了初步的有力证据，药用植物含有柠檬苦素，Tangeritin，6-姜酚，Zerumbone，灵芝酸A，灵芝酸DM可以应用于高级别脑膜瘤作为一种治疗剂，并表明，进一步的体内研究是必要的，以探索其作为一种治疗剂对恶性脑膜瘤的潜力。
Recurrent meningiomas constitute an uncommon but significant problem after standard (surgery and radiation) therapy failure. Current chemotherapies (hydroxyurea, RU-486, and interferon-α) are only of marginal benefit. There is an urgent need for more effective treatments for meningioma patients who have failed surgery and radiation therapy. Limonin, Tangeritin, Zerumbone, 6-Gingerol, Ganoderic Acid A, and Ganoderic Acid DM are some of the plant derivatives that have anti-tumorgenic properties and cause cell death in meningioma cells in vitro. Due to its ease of administration, long-term tolerability, and low incidence of long-term side effects, we explored its potential as a therapeutic agent against meningiomas by examining their efficacy in vitro against meningioma cells. Treatment effects were assessed using MTT assay, Western blot analysis, caspases assay, and DNA fragmentation assay. Results indicated that treatments of IOMM-Lee and CH157MN meningioma cells with Limonin, Tangeritin, Zerumbone, 6-Gingerol, Ganoderic Acid A, and Ganoderic Acid DM induced apoptosis with enhanced phosphorylation of glycogen synthase kinase 3 β (GSK3β) via inhibition of the Wnt5/β-catenin pathway. These drugs did not induce apoptosis in normal human neurons. Other events in apoptosis included downregulation of tetraspanin protein (TSPAN12), survival proteins (Bcl-XL and Mcl-1), and overexpression apoptotic factors (Bax and caspase-3). These results provide preliminary strong evidence that medicinal plants containing Limonin, Tangeritin, 6-Gingerol, Zerumbone, Ganoderic Acid A, and Ganoderic Acid DM can be applied to high-grade meningiomas as a therapeutic agent, and suggests that further in vivo studies are necessary to explore its potential as a therapeutic agent against malignant meningiomas.
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影响因子：
8
作者：
Knoblich, Konstantin;Wang, Hong-Xing;Hemler, Martin E.
通讯作者：
Hemler, Martin E.
影响因子：
--
作者：
Ragel, Brian T.;Couldwell, William T.;Jensen, Randy L.
通讯作者：
Jensen, Randy L.
影响因子：
1.3
作者：
Liu, Liqiong;Stone, Jonathan;Xiong, Zhenggang
通讯作者：
Xiong, Zhenggang
影响因子：
4
作者：
Metcalfe, Ciara;Bienz, Mariann
通讯作者：
Bienz, Mariann
DOI：
10.1016/j.ijrobp.2007.12.020
发表时间：
2008-08-01
影响因子：
7
作者：
Pasquier, David;Bijmolt, Stefan;Mirimanoff, Rene O.
通讯作者：
Mirimanoff, Rene O.