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

This is the authors' abstract. We don't add key points for this paper.

// Sun-Yong Kim 1 , Haeng-Jun Kim 1, 2 , Sung Un Kang 1 , Yang Eun Kim 1, 2 , Ju Kyeong Park 1, 2 , Yoo Seob Shin 1 , Yeon Soo Kim 1 , Keunho Lee 3 , Chul-Ho Kim 1, 2 1 Department of Otolaryngology, Ajou University School of Medicine, Suwon, Republic of Korea 2 Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea 3 PSM America Inc., Colorado Springs, CO, USA Correspondence to: Chul-Ho Kim, e-mail: ostium@ajou.ac.kr Keywords: non-thermal plasma (NTP), head and neck cancer (HNC), AKT ubiquitination, liquid type plasma (LTP), mitochondrial E3 ubiquitin protein ligase 1 (MUL1) Received: June 23, 2015 Accepted: September 18, 2015 Published: September 30, 2015 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.