Non-thermal atmospheric pressure plasma induces apoptosis in oral cavity squamous cell carcinoma: Involvement of DNA-damage-triggering sub-G(1) arrest via the ATM/p53 pathway.
Recent advances in physics have made possible the use of non-thermal atmospheric pressure plasma (NTP) in cancer research. Although increasing evidence suggests that NTP induces death of various cancer cell types, thus offering a promising alternative treatment, the mechanism of its therapeutic effect is little understood. In this study, we report for the first time that NTP led to apoptotic cell death in oral cavity squamous cell carcinoma (OSCC). Interestingly, NTP induced a sub-G(1) arrest in p53 wild-type OSCCs, but not in p53-mutated OSCCs. In addition, NTP increased the expression levels of ATM, p53 (Ser 15, 20 and 46), p21, and cyclin D1. A comet assay, Western blotting and immunocytochemistry of γH2AX suggested that NTP-induced apoptosis and sub-G(1) arrest were associated with DNA damage and the ATM/p53 signaling pathway in SCC25 cells. Moreover, ATM knockdown using siRNA attenuated the effect of NTP on cell death, sub-G(1) arrest and related signals. Taken together, these results indicate that NTP induced apoptotic cell death in p53 wild-type OSCCs through a novel mechanism involving DNA damage and triggering of sub-G(1) arrest via the ATM/p53 pathway. These findings show the therapeutic potential of NTP in OSCC.
Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Gyounggi-Do, Republic of Korea.
Jae Won
JW
Chang
Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Gyounggi-Do, Republic of Korea.
Sung Un
SU
Kang
Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Gyounggi-Do, Republic of Korea.
Yoo Seob
YS
Shin
Department of Electrical and Computer Engineering, Ajou University, Suwon, Gyounggi-Do, Republic of Korea.
Kang Il
KI
Kim
Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Gyounggi-Do, Republic of Korea.
Seong Jin
SJ
Seo
Department of Electrical and Computer Engineering, Ajou University, Suwon, Gyounggi-Do, Republic of Korea.
Sang Sik
SS
Yang
Department of Molecular Science and Technology and Department of Life Science, Ajou University, Suwon, Gyounggi-Do, Republic of Korea.
Jong-Soo
JS
Lee
Department of Molecular Science and Technology and Department of Life Science, Ajou University, Suwon, Gyounggi-Do, Republic of Korea.
Eunpyo
E
Moon
Department of Otolaryngology-Head and Neck Surgery, Yonsei University Wonju College of Medicine, Wonju, Gangwon-Do, Republic of Korea.
Seung Jae
SJ
Baek
PSM America Inc., Colorado Springs, CO, USA.
Keunho
K
Lee
Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Gyounggi-Do, Republic of Korea. Electronic address: ostium@ajou.ac.kr.
Chul-Ho
CH
Kim
D017209:Apoptosis; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D045744:Cell Line, Tumor; D004249:DNA Damage; D059585:G1 Phase Cell Cycle Checkpoints; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D009154:Mutation; D058626:Plasma Gases / Q000494:pharmacology*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D058626:Plasma Gases; D016159:Tumor Suppressor Protein p53; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins
Ataxia telangiectasia mutated (ATM); DNA damage; Non-thermal atmospheric pressure plasma (NTP); Oral cavity squamous cell carcinoma (OSCC); Sub-G(1) arrest; p53