title: Non-thermal plasma induces AKT degradation through turn-on the MUL1 E3 ligase in head and neck cancer.
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.
authors.affiliation: Department of Otolaryngology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Sun-Yong
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Otolaryngology, Ajou University School of Medicine, Suwon, Republic of Korea.|Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea.
authors.forename: Haeng-Jun
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Otolaryngology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Sung Un
authors.initials: SU
authors.lastname: Kang
authors.affiliation: Department of Otolaryngology, Ajou University School of Medicine, Suwon, Republic of Korea.|Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea.
authors.forename: Yang Eun
authors.initials: YE
authors.lastname: Kim
authors.affiliation: Department of Otolaryngology, Ajou University School of Medicine, Suwon, Republic of Korea.|Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea.
authors.forename: Ju Kyeong
authors.initials: JK
authors.lastname: Park
authors.affiliation: Department of Otolaryngology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Yoo Seob
authors.initials: YS
authors.lastname: Shin
authors.affiliation: Department of Otolaryngology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Yeon Soo
authors.initials: YS
authors.lastname: Kim
authors.affiliation: PSM America Inc., Colorado Springs, CO, USA.
authors.forename: Keunho
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Otolaryngology, Ajou University School of Medicine, Suwon, Republic of Korea.|Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea.
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Kim
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D024101:Mitochondrial Proteins / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D058626:Plasma Gases / Q000494:pharmacology*; D059748:Proteolysis / Q000187:drug effects*; D034741:RNA, Small Interfering / Q000494:pharmacology; D000077195:Squamous Cell Carcinoma of Head and Neck; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D024101:Mitochondrial Proteins; D058626:Plasma Gases; D034741:RNA, Small Interfering; C000608240:MUL1 protein, mouse; D044767:Ubiquitin-Protein Ligases; D051058:Oncogene Protein v-akt
keywords: AKT ubiquitination; head and neck cancer (HNC); liquid type plasma (LTP); mitochondrial E3 ubiquitin protein ligase 1 (MUL1); non-thermal plasma (NTP)