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首页> 外文期刊>Drug Target Insights >Repercussion of Mitochondria Deformity Induced by Anti-Hsp90 Drug 17AAG in Human Tumor Cells
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Repercussion of Mitochondria Deformity Induced by Anti-Hsp90 Drug 17AAG in Human Tumor Cells

机译：抗Hsp90药物17AAG诱导人肿瘤细胞线粒体畸形的影响

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Inhibiting Hsp90 chaperone roles using 17AAG induces cytostasis or apoptosis in tumor cells through destabilization of several mutated cancer promoting proteins. Although mitochondria are central in deciding the fate of cells, 17AAG induced effects on tumor cell mitochondria were largely unknown. Here, we show that Hsp90 inhibition with 17AAG first affects mitochondrial integrity in different human tumor cells, neuroblastoma, cervical cancer and glial cells. Using human neuroblastoma tumor cells, we found the early effects associated with a change in mitochondrial membrane potential, elongation and engorgement of mitochondria because of an increased matrix vacuolization. These effects are specific to Hsp90 inhibition as other chemotherapeutic drugs did not induce similar mitochondrial deformity. Further, the effects are independent of oxidative damage and cytoarchitecture destabilization since cytoskeletal disruptors and mitochondrial metabolic inhibitors also do not induce similar deformity induced by 17AAG. The 1D PAGE LC MS/MS mitochondrial proteome analysis of 17AAG treated human neuroblastoma cells showed a loss of 61% proteins from membrane, metabolic, chaperone and ribonucleoprotein families. About 31 unmapped protein IDs were identified from proteolytic processing map using Swiss-Prot accession number, and converted to the matching gene name searching the ExPASy proteomics server. Our studies display that Hsp90 inhibition effects at first embark on mitochondria of tumor cells and compromise mitochondrial integrity.
机译：使用17AAG抑制Hsp90分子伴侣的作用通过使几种突变的促癌蛋白不稳定来诱导肿瘤细胞的细胞停滞或凋亡。尽管线粒体是决定细胞命运的关键，但17AAG诱导的对肿瘤细胞线粒体的作用尚不清楚。在这里，我们表明用17AAG抑制Hsp90首先会影响不同人类肿瘤细胞，神经母细胞瘤，宫颈癌和神经胶质细胞的线粒体完整性。使用人类神经母细胞瘤肿瘤细胞，我们发现由于基质空泡增加，与线粒体膜电位变化，线粒体伸长和充血有关的早期影响。这些作用对Hsp90抑制具有特异性，因为其他化疗药物未诱导类似的线粒体畸形。此外，该作用与氧化损伤和细胞结构失稳无关，因为细胞骨架破坏剂和线粒体代谢抑制剂也不会引起17AAG诱导的类似畸形。对17AAG处理的人成神经细胞瘤细胞进行的一维PAGE LC MS / MS线粒体蛋白质组分析显示，膜，代谢，伴侣和核糖核蛋白家族中的蛋白质损失了61％。使用Swiss-Prot登录号从蛋白水解加工图中鉴定出约31个未映射的蛋白质ID，并将其转换为匹配的基因名称，以搜索ExPASy蛋白质组学服务器。我们的研究表明，Hsp90抑制作用首先会影响肿瘤细胞的线粒体并损害线粒体的完整性。

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