Non-thermal atmospheric pressure plasma preferentially induces apoptosis in p53-mutated cancer cells by activating ROS stress-response pathways.
Non-thermal atmospheric pressure plasma (NTAPP) is an ionized gas at room temperature and has potential as a new apoptosis-promoting cancer therapy that acts by generating reactive oxygen species (ROS). However, it is imperative to determine its selectivity and standardize the components and composition of NTAPP. Here, we designed an NTAPP-generating apparatus combined with a He gas feeding system and demonstrated its high selectivity toward p53-mutated cancer cells. We first determined the proper conditions for NTAPP exposure to selectively induce apoptosis in cancer cells. The apoptotic effect of NTAPP was greater for p53-mutated cancer cells; artificial p53 expression in p53-negative HT29 cells decreased the pro-apoptotic effect of NTAPP. We also examined extra- and intracellular ROS levels in NTAPP-treated cells to deduce the mechanism of NTAPP action. While NTAPP-mediated increases in extracellular nitric oxide (NO) did not affect cell viability, intracellular ROS increased under NTAPP exposure and induced apoptotic cell death. This effect was dose-dependently reduced following treatment with ROS scavengers. NTAPP induced apoptosis even in doxorubicin-resistant cancer cell lines, demonstrating the feasibility of NTAPP as a potent cancer therapy. Collectively, these results strongly support the potential of NTAPP as a selective anticancer treatment, especially for p53-mutated cancer cells.
Department of Biochemistry, College of Life Science & Biotechnology, Yonsei University, Seoul, Korea.
Yonghao
Y
Ma
Department of Electrical Engineering, Pusan National University, Pusan, Korea.
Chang Seung
CS
Ha
Department of Electrical Engineering, Pusan National University, Pusan, Korea.
Seok Won
SW
Hwang
Department of Electrical Engineering, Pusan National University, Pusan, Korea.
Hae June
HJ
Lee
Department of Oral Anatomy, School of Dentistry, Pusan National University, Yangsan, Korea.
Gyoo Cheon
GC
Kim
Department of Obstetrics and Gynecology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Kyo-Won
KW
Lee
Department of Biochemistry, College of Life Science & Biotechnology, Yonsei University, Seoul, Korea.
Kiwon
K
Song
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D019073:HT29 Cells; D006801:Humans; D058626:Plasma Gases / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D058626:Plasma Gases; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53