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

作者：Kim Sun Yong; Kim Haeng Jun; Kang Sung Un; Kim Yang Eun; Park Ju Kyeong; Shin Yoo Seob; Kim Yeon Soo; Lee Keunho; Kim Chul Ho^*

来源：Oncotarget, 2015, 6(32): 33382-33396.

DOI：10.18632/oncotarget.5407

• non-thermal plasma (NTP)
• head and neck cancer (HNC)
• AKT ubiquitination
• liquid type plasma (LTP)
• mitochondrial E3 ubiquitin protein ligase 1 (MUL1)

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.

• 出版日期2015-10-20