Physical plasma-triggered ROS induces tumor cell death upon cleavage of HSP90 chaperone
Physical plasma-triggered ROS induces tumor cell death upon cleavage of HSP90 chaperone
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DOI：
10.1038/s41598-019-38580-0
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发表时间：
2019-03-11
影响因子：
4.6
通讯作者：
Azoitei, Ninel
中科院分区：
文献类型：
--
作者：
Bekeschus, Sander;Lippert, Maxi;Azoitei, Ninel
HSP 90是一种广泛表达的分子伴侣，参与包括蛋白激酶和转录因子在内的多种蛋白质的正确折叠和成熟。虽然伴侣活性的破坏与体外和体内的癌细胞死亡增加和肿瘤生长减少有关，但对HSP 90的调控尚不清楚。在这里，我们报告了用冷物理等离子体治疗癌细胞，一种新兴的和侵略性较低的肿瘤治疗，导致ROS的产生，随后触发HSP 90的切割。值得注意的是，HSP 90的裂解之后是PKD 2的降解，PKD 2是肿瘤生长和血管生成的关键调节因子。用阈下剂量的PU-H71（一种目前正在临床评估的HSP 90抑制剂）对癌细胞进行预致敏，然后用冷等离子体处理，对癌细胞的活力产生协同和负面影响。总之，冷等离子体可以与药物治疗结合使用，以靶向HSP 90和涉及各种癌细胞能力的下游客户蛋白的表达和活性。
HSP90 is a ubiquitously expressed molecular chaperone implicated in the correct folding and maturation of a plethora of proteins including protein kinases and transcription factors. While disruption of chaperone activity was associated with augmented cancer cell death and decreased tumor growth both in vitro and in vivo, the regulation of HSP90 is not clearly understood. Here we report that treatment of cancer cells with cold physical plasma, an emerging and less aggressive tumor therapy, resulted in ROS generation which subsequently triggered the cleavage of HSP90. Notably, cleavage of HSP90 was followed by the degradation of PKD2, a crucial regulator of tumor growth and angiogenesis. Pre-sensitization of cancer cells with subliminal doses of PU-H71, an HSP90 inhibitor currently under clinical evaluation, followed by treatment with cold-plasma, synergistically and negatively impacted on the viability of cancer cells. Taken together, cold-plasma can be used in conjunction with pharmacologic treatment in order to target the expression and activity of HSP90 and the downstream client proteins implicated in various cancer cell capabilities.