Englerin a selectively induces necrosis in human renal cancer cells.
Englerin a selectively induces necrosis in human renal cancer cells.
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DOI：
10.1371/journal.pone.0048032
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ramos JW
中科院分区：
文献类型：
--
作者：
Sulzmaier FJ;Li Z;Nakashige ML;Fash DM;Chain WJ;Ramos JW
肾癌的数量在过去十年中有所增加，晚期患者的存活率仍然很低。因此，新的肾癌治疗方法是必不可少的。Englerin A是一种天然产物，对肾癌细胞具有非常有效和选择性的细胞毒性。这使其成为一种有希望的候选药物，可以改善所有阶段肾癌患者的当前治疗标准。然而，关于englerin A在特异性靶向肾癌细胞中的作用模式知之甚少。我们的研究是第一个详细研究englerin A作用的生物学机制。我们报道englerin A对肾肿瘤细胞具有特异性，并且不影响正常肾细胞。我们发现englerin A处理诱导肾癌细胞的坏死细胞死亡，但在正常肾细胞中不诱导。我们进一步表明，自噬和pyroptotic蛋白是不受化合物和坏死信号在这些细胞中的生产与活性氧和钙离子流入细胞质。作为第一个分析englerin A生物学效应的研究，我们的工作为评价和验证该化合物作为抗肿瘤药物的用途提供了重要依据。它还提供了一种环境，在其中鉴定肾癌细胞中englerin A的一个或多个特定靶标。
The number of renal cancers has increased over the last ten years and patient survival in advanced stages remains very poor. Therefore, new therapeutic approaches for renal cancer are essential. Englerin A is a natural product with a very potent and selective cytotoxicity against renal cancer cells. This makes it a promising drug candidate that may improve current treatment standards for patients with renal cancers in all stages. However, little is known about englerin A's mode of action in targeting specifically renal cancer cells. Our study is the first to investigate the biological mechanism of englerin A action in detail. We report that englerin A is specific for renal tumor cells and does not affect normal kidney cells. We find that englerin A treatment induces necrotic cell death in renal cancer cells but not in normal kidney cells. We further show that autophagic and pyroptotic proteins are unaffected by the compound and that necrotic signaling in these cells coincided with production of reactive oxygen species and calcium influx into the cytoplasm. As the first study to analyze the biological effects of englerin A, our work provides an important basis for the evaluation and validation of the compound's use as an anti-tumor drug. It also provides a context in which to identify the specific target or targets of englerin A in renal cancer cells.
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DOI：
10.1073/pnas.93.20.10595
发表时间：
1996-10-01
影响因子：
11.1
作者：
Iliopoulos, O;Levy, AP;Goldberg, MA
通讯作者：
Goldberg, MA
影响因子：
4.8
作者：
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影响因子：
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作者：
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影响因子：
45.3
作者：
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通讯作者：
Reichman, Marsha E.
影响因子：
5.7
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Ikediobi ON;Davies H;Bignell G;Edkins S;Stevens C;O'Meara S;Santarius T;Avis T;Barthorpe S;Brackenbury L;Buck G;Butler A;Clements J;Cole J;Dicks E;Forbes S;Gray K;Halliday K;Harrison R;Hills K;Hinton J;Hunter C;Jenkinson A;Jones D;Kosmidou V;Lugg R;Menzies A;Mironenko T;Parker A;Perry J;Raine K;Richardson D;Shepherd R;Small A;Smith R;Solomon H;Stephens P;Teague J;Tofts C;Varian J;Webb T;West S;Widaa S;Yates A;Reinhold W;Weinstein JN;Stratton MR;Futreal PA;Wooster R
通讯作者：
Wooster R