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: Sun-Yong Kim, Haeng-Jun Kim, Sung Un Kang, Yang Eun Kim, Ju Kyeong Park, Yoo Seob Shin, Yeon Soo Kim, Keunho Lee, Chul-Ho Kim
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 32 Pg. 33382-96 (Oct 20 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 26450902 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Mitochondrial Proteins
• Plasma Gases
• RNA, Small Interfering
• MUL1 protein, mouse
• Ubiquitin-Protein Ligases
• Oncogene Protein v-akt

Topics

• Animals
• Carcinoma, Squamous Cell (genetics, metabolism, pathology)
• Cell Line, Tumor
• Enzyme Activation (drug effects)
• Gene Expression Regulation, Enzymologic (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Head and Neck Neoplasms (genetics, metabolism, pathology)
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Mitochondrial Proteins (agonists, antagonists & inhibitors, genetics, metabolism)
• Oncogene Protein v-akt (metabolism)
• Plasma Gases (pharmacology)
• Proteolysis (drug effects)
• RNA, Small Interfering (pharmacology)
• Squamous Cell Carcinoma of Head and Neck
• Ubiquitin-Protein Ligases (antagonists & inhibitors, genetics, metabolism)
• Xenograft Model Antitumor Assays