Physical plasma-triggered ROS induces tumor cell death upon cleavage of HSP90 chaperone View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Sander Bekeschus, Maxi Lippert, Kristina Diepold, Gabriela Chiosis, Thomas Seufferlein, Ninel Azoitei

ABSTRACT

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. More... »

PAGES

4112

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-019-38580-0

DOI

http://dx.doi.org/10.1038/s41598-019-38580-0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112678819

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30858416


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