期刊
ONCOTARGET
卷 6, 期 32, 页码 33382-33396出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.5407
关键词
non-thermal plasma (NTP); head and neck cancer (HNC); AKT ubiquitination; liquid type plasma (LTP); mitochondrial E3 ubiquitin protein ligase 1 (MUL1)
资金
- Bio & Medical Technology Development Program [2012M3A9B2052870]
- ICT and future Planning of the National Research Foundation of Korea (NRF) - Ministry of Science [2015R1A2A1A01002968]
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [2014R1A1A2059746]
- National Research Foundation of Korea [2015R1A2A1A01002968, 2014R1A1A2059746] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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.
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