Inhibitors of cathepsins B and L induce autophagy and cell death in neuroblastoma cells.
Inhibitors of cathepsins B and L induce autophagy and cell death in neuroblastoma cells.
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DOI：
10.1007/s10637-012-9826-6
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发表时间：
2013-02
影响因子：
3.4
通讯作者：
Mason, Robert W.
中科院分区：
文献类型：
--
作者：
Cartledge, Donna M.;Colella, Rita;Glazewski, Lisa;Lu, Guizhen;Mason, Robert W.
本研究旨在验证特异性抑制组织蛋白酶B和L会导致神经母细胞瘤细胞死亡的假设。这两种酶的抑制模式和速率不同的五种化合物均显示引起神经母细胞瘤细胞死亡。不同化合物的功效与它们抑制分离的酶的活性的能力有关。证明了每种化合物诱导细胞死亡的剂量和时间响应。蛋白质组学研究表明，抑制剂处理引起细胞应激标志物的增加，包括诱导自噬标志物LC-3-II的水平。这种标志物蛋白的水平在细胞毒性抑制剂浓度下最高，暗示细胞死亡过程中的自噬。体内小鼠模型表明，这些抑制剂之一显着损害肿瘤生长。结论是，开发针对这两种蛋白酶的药物可能为治疗神经母细胞瘤提供一种新的方法。
This study was designed to test the hypothesis that specific inhibition of cathepsins B and L will cause death of neuroblastoma cells. Five compounds that differ in mode and rate of inhibition of these two enzymes were all shown to cause neuroblastoma cell death. Efficacy of the different compounds was related to their ability to inhibit the activity of the isolated enzymes. A dose- and time-response for induction of cell death was demonstrated for each compound. A proteomic study showed that inhibitor treatment caused an increase of markers of cell stress, including induction of levels of the autophagy marker, LC-3-II. Levels of this marker protein were highest at cytotoxic inhibitor concentrations, implicating autophagy in the cell death process. An in vivo mouse model showed that one of these inhibitors markedly impaired tumor growth. It is concluded that development of drugs to target these two proteases may provide a novel approach to treating neuroblastoma.
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影响因子：
4.1
作者：
MASON, RW;GREEN, GDJ;BARRETT, AJ
通讯作者：
BARRETT, AJ
DOI：
10.1007/978-1-4419-8414-2_7
发表时间：
2011-01-01
期刊：
CYSTEINE PROTEASES OF PATHOGENIC ORGANISMS
影响因子：
--
作者：
Sajid, Mohammed;Robertson, Stephanie A.;McKerrow, James H.
通讯作者：
McKerrow, James H.
DOI：
10.1016/j.bbrc.2007.11.104
发表时间：
2008-02-01
影响因子：
3.1
作者：
Anagli, John;Abounit, Kadija;Seyfried, Donald
通讯作者：
Seyfried, Donald
影响因子：
64.8
作者：
Mosse, Yael P.;Laudenslager, Marci;Longo, Luca;Cole, Kristina A.;Wood, Andrew;Attiyeh, Edward F.;Laquaglia, Michael J.;Sennett, Rachel;Lynch, Jill E.;Perri, Patrizia;Laureys, Genevieve;Speleman, Frank;Kim, Cecilia;Hou, Cuiping;Hakonarson, Hakon;Torkamani, Ali;Schork, Nicholas J.;Brodeur, Garrett M.;Tonini, Gian P.;Rappaport, Eric;Devoto, Marcella;Maris, John M.
通讯作者：
Maris, John M.
影响因子：
158.5
作者：
Matthay, KK;Villablanca, JG;Reynolds, CP
通讯作者：
Reynolds, CP