Hippuristanol reduces the viability of primary effusion lymphoma cells both in vitro and in vivo.
Hippuristanol reduces the viability of primary effusion lymphoma cells both in vitro and in vivo.
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DOI：
10.3390/md11093410
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发表时间：
2013-09-06
期刊：
影响因子：
5.4
通讯作者：
Mori N
中科院分区：
文献类型：
--
作者：
Ishikawa C;Tanaka J;Katano H;Senba M;Mori N
原发性渗出性淋巴瘤（PEL）是由卡波西肉瘤相关疱疹病毒（也称为人类疱疹病毒-8）引起的，表现为体腔内严重的淋巴瘤性渗出。PEL很难治疗，没有标准的治疗策略。从冲绳珊瑚Isis hippuris中提取的马尿酸，通过阻断真核起始因子4A（一种ATP依赖性RNA解旋酶）与mRNA的结合来抑制翻译起始。近年来，人们对靶向翻译起始作为抗癌疗法产生了很大的兴趣。在这里，我们表明，治疗的PEL细胞系与马尿酸导致细胞周期停滞在G1期，并诱导半胱天冬酶激活和凋亡。马尿酸还降低了细胞周期蛋白D2、CDK 2、CDK 4、CDK 6和促生存XIAP和Mcl-1蛋白的表达。激活蛋白-1、信号转导和转录激活蛋白3以及Akt通路的激活在PEL细胞的存活和生长中起关键作用。马尿酸通过抑制JunB、JunD、c-Fos、信号转导与转录激活蛋白3和Akt蛋白的表达，抑制上述3条通路的活性。在一个异种移植小鼠模型，显示腹水和弥漫性器官侵入的PEL细胞，与未经处理的小鼠相比，治疗与马尿酸显着抑制的PEL细胞的生长和侵袭。体外和体内实验的结果强调了马尿酸在治疗PEL中的潜在用途。
Primary effusion lymphoma (PEL) caused by Kaposi’s sarcoma-associated herpesvirus (also known as human herpesvirus-8) shows serious lymphomatous effusion in body cavities. PEL is difficult to treat and there is no standard treatment strategy. Hippuristanol is extracted from Okinawan coral Isis hippuris, and inhibits translational initiation by blocking eukaryotic initiation factor 4A, an ATP-dependent RNA helicase, binding to mRNA. Recently, there has been much interest in targeting translation initiation as an anticancer therapy. Here, we show that treatment of PEL cell lines with hippuristanol resulted in cell cycle arrest at G1 phase, and induced caspases activation and apoptosis. Hippuristanol also reduced the expression of cyclin D2, CDK2, CDK4, CDK6 and prosurvival XIAP and Mcl-1 proteins. Activation of activator protein-1, signal transducers and activators of transcription protein 3 and Akt pathways plays a critical role in the survival and growth of PEL cells. Hippuristanol suppressed the activities of these three pathways by inhibiting the expression of JunB, JunD, c-Fos, signal transducers and activators of transcription protein 3 and Akt proteins. In a xenograft mouse model that showed ascites and diffused organ invasion of PEL cells, treatment with hippuristanol significantly inhibited the growth and invasion of PEL cells compared with untreated mice. The results of the in vitro and in vivo experiments underline the potential usefulness of hippuristanol in the treatment of PEL.
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影响因子：
64.5
作者：
Chakraborty A;Koldobskiy MA;Bello NT;Maxwell M;Potter JJ;Juluri KR;Maag D;Kim S;Huang AS;Dailey MJ;Saleh M;Snowman AM;Moran TH;Mezey E;Snyder SH
通讯作者：
Snyder SH
影响因子：
15.9
作者：
Epling-Burnette, PK;Liu, JH;Loughran, TP
通讯作者：
Loughran, TP
影响因子：
45.3
作者：
Boulanger, E;Gérard, L;Oksenhendler, E
通讯作者：
Oksenhendler, E
影响因子：
--
作者：
Michai, Manthana;Goto, Hiroki;Okada, Seiji
通讯作者：
Okada, Seiji
DOI：
10.4049/jimmunol.0903025
发表时间：
2010-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Chan G;Nogalski MT;Bentz GL;Smith MS;Parmater A;Yurochko AD
通讯作者：
Yurochko AD