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Non-thermal plasma induces AKT degradation through turn-on the MUL1 E3 ligase in head and neck cancer.

Authors
Kim, SY  | Kim, HJ | Kang, SU  | Kim, YE | Park, JK | Shin, YS  | Kim, YS  | Lee, K | Kim, CH
Citation
Oncotarget, 6(32). : 33382-33396, 2015
Journal Title
Oncotarget
ISSN
1949-2553
Abstract
Recent research on non-thermal plasma (NTP, an ionized gas) has identified it as a novel cancer therapeutic tool. However, the molecular mechanism remains unclear. In this study, we demonstrated NTP induced cell death of head and neck cancer (HNC) through the AKT ubiquitin-proteasome system. NTP increased the gene expression of mitochondrial E3 ubiquitin protein ligase 1 (MUL1), an E3 ligase for AKT, and NTP-induced HNC cell death was prevented by MUL1 siRNA. We also showed that MUL1 inhibited the level of AKT and p-AKT and MUL1 expression was increased by NTP-induced ROS. Furthermore, we optimized and manufactured a new type of NTP, a liquid type of NTP (LTP). In syngeneic and xenograft in vivo tumor models, LTP inhibited tumor progression by increasing the MUL1 level and reducing p-AKT levels, indicating that LTP also has an anti-cancer effect through the same mechanism as that of NTP. Taken together, our results suggest that NTP and LTP have great potential for HNC therapy.
MeSH

DOI
10.18632/oncotarget.5407
PMID
26450902
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Otolaryngology
Ajou Authors
강, 성운  |  김, 선용  |  김, 연수  |  김, 철호  |  신, 유섭
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