Disulfiram suppresses growth of the malignant pleural mesothelioma cells in part by inducing apoptosis.
Disulfiram suppresses growth of the malignant pleural mesothelioma cells in part by inducing apoptosis.
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DOI：
10.1371/journal.pone.0093711
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Rishi AK
中科院分区：
文献类型：
--
作者：
Cheriyan VT;Wang Y;Muthu M;Jamal S;Chen D;Yang H;Polin LA;Tarca AL;Pass HI;Dou QP;Sharma S;Wali A;Rishi AK
二硫代氨基甲酸盐化合物双硫仑 (DSF) 与铜结合并充当乙醛脱氢酶抑制剂，是美国食品和药物管理局批准的治疗酒精中毒的药物。铜络合 DSF (DSF-Cu) 还具有抗肿瘤和化学增敏特性；然而，其分子作用机制仍不清楚。在这里，我们研究了 DSF-Cu 的恶性胸膜间皮瘤 (MPM) 抑制作用及其分子机制。 DSF-Cu 部分通过增加泛素化蛋白的水平来抑制小鼠和人类 MPM 细胞的生长。 DSF-Cu 暴露刺激 MPM 细胞凋亡，涉及应激激活蛋白激酶 (SAPK) p38 和 JNK1/2、caspase-3 的激活和聚（ADP-核糖）聚合酶的裂解，以及硫酸酯酶 1 和凋亡转导 CARP-1/CCAR1 蛋白表达的增加。基于基因阵列的分析显示，DSF-Cu 抑制细胞生长和促进转移的基因，包括基质金属肽酶 3 和 10。DSF 通过上调细胞周期抑制剂 p27Kip1、IGFBP7 以及 NF-κB 抑制剂（例如 ABIN 1 和 2 以及抑制性 κB (IκB)α 和 β 蛋白）来抑制 MPM 细胞生长和存活。 DSF-Cu 促进波形蛋白的裂解，以及平足蛋白的丝氨酸磷酸化和赖氨酸 63 连接的泛素化。每日腹腔注射 50 mg/kg DSF-Cu 可抑制体内小鼠 MPM 细胞衍生肿瘤的生长。尽管平足蛋白表达通常与转移性疾病和不良预后相关，但平足蛋白细胞质结构域中丝氨酸的磷酸化最近已被证明会干扰细胞运动和迁移信号传导。 DSF-Cu 对足足蛋白的翻译后修饰和波形蛋白的裂解强调了该药物的转移抑制特性，并与我们的体内研究一起强调了其作为抗 MPM 药物的潜力。
Dithiocarbamate compound Disulfiram (DSF) that binds with copper and functions as an inhibitor of aldehyde dehydrogenase is a Food and Drug Administration approved agent for treatment of alcoholism. Copper complexed DSF (DSF-Cu) also possesses anti-tumor and chemosensitizing properties; however, its molecular mechanisms of action remain unclear. Here we investigated malignant pleural mesothelioma (MPM) suppressive effects of DSF-Cu and the molecular mechanisms involved. DSF-Cu inhibited growth of the murine as well as human MPM cells in part by increasing levels of ubiquitinated proteins. DSF-Cu exposure stimulated apoptosis in MPM cells that involved activation of stress-activated protein kinases (SAPKs) p38 and JNK1/2, caspase-3, and cleavage of poly-(ADP-ribose)-polymerase, as well as increased expression of sulfatase 1 and apoptosis transducing CARP-1/CCAR1 protein. Gene-array based analyses revealed that DSF-Cu suppressed cell growth and metastasis-promoting genes including matrix metallopeptidase 3 and 10. DSF inhibited MPM cell growth and survival by upregulating cell cycle inhibitor p27Kip1, IGFBP7, and inhibitors of NF-κB such as ABIN 1 and 2 and Inhibitory κB (IκB)α and β proteins. DSF-Cu promoted cleavage of vimentin, as well as serine-phosphorylation and lysine-63 linked ubiquitination of podoplanin. Administration of 50 mg/kg DSF-Cu by daily i.p injections inhibited growth of murine MPM cell-derived tumors in vivo. Although podoplanin expression often correlates with metastatic disease and poor prognosis, phosphorylation of serines in cytoplasmic domain of podoplanin has recently been shown to interfere with cellular motility and migration signaling. Post-translational modification of podoplanin and cleavage of vimentin by DSF-Cu underscore a metastasis inhibitory property of this agent and together with our in vivo studies underscore its potential as an anti-MPM agent.
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影响因子：
3.7
作者：
Ashour AE;Jamal S;Cheryan VT;Muthu M;Zoheir KM;Alafeefy AM;Abd-Allah AR;Levi E;Tarca AL;Polin LA;Rishi AK
通讯作者：
Rishi AK
影响因子：
8.8
作者：
Liu, P.;Kumar, I. S.;Brown, S.;Kannappan, V.;Tawari, P. E.;Tang, J. Z.;Jiang, W.;Armesilla, A. L.;Darling, J. L.;Wang, W.
通讯作者：
Wang, W.
石棉引起的肺部疾病：更新。
DOI：
10.1016/j.trsl.2009.01.004
发表时间：
2009-04
期刊：
Translational research : the journal of laboratory and clinical medicine
影响因子：
--
作者：
Kamp DW
通讯作者：
Kamp DW
影响因子：
3.3
作者：
Martín-Villar E;Fernández-Muñoz B;Parsons M;Yurrita MM;Megías D;Pérez-Gómez E;Jones GE;Quintanilla M
通讯作者：
Quintanilla M
影响因子：
7.3
作者：
Brahemi G;Kona FR;Fiasella A;Buac D;Soukupová J;Brancale A;Burger AM;Westwell AD
通讯作者：
Westwell AD