Cold atmospheric plasma induces GSDME-dependent pyroptotic signaling pathway via ROS generation in tumor cells

• Published in: Cell death & disease Vol. 11; no. 4; p. 295
• Main Authors: Yang, Xiaorui, Chen, Guodong, Yu, Kwan Ngok, Yang, Miaomiao, Peng, Shengjie, Ma, Jie, Qin, Feng, Cao, Wei, Cui, Shujun, Nie, Lili, Han, Wei
• Format: Journal Article
• Language: English
• Published: England Springer Nature B.V 27.04.2020; Nature Publishing Group UK
• Subjects: Apoptosis; Cancer; Cancer therapies; Caspase-3; Caspase-9; Cell Death; Cell Line, Tumor; Cytochrome c; Humans; Mitochondria; Plasma Gases - metabolism; Pyroptosis; Pyroptosis - genetics; Reactive Oxygen Species - metabolism; Receptors, Estrogen - metabolism; Signal Transduction; Transfection; Tumor cell lines; Tumor cells
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-020-2459-3

Cold atmospheric plasma (CAP) has been proposed as a novel promising anti-cancer treatment modality. Apoptosis and necrosis have been revealed in CAP-induced cell death, but whether CAP induces pyroptosis, another kind of programmed cell death is still unknown. In the present study, we first reported that CAP effectively induced pyroptosis in a dose-dependent manner in Gasdermin E (GSDME) high-expressed tumor cell lines. Interestingly, the basal level of GSDME protein was positively correlated with the sensitivity to CAP in three selected cancer cell lines, implying GSDME might be a potential biomarker of prognosis in the forthcoming cancer CAP treatment. Moreover, our study revealed that CAP-induced pyroptosis depended on the activation of mitochondrial pathways (JNK/cytochrome c/caspase-9/caspase-3) and the cleavage of GSDME but not Gasdermin D (GSDMD). ROS generation induced by CAP was identified to initiate the pyroptotic signaling. These results complemented our knowledge on CAP-induced cell death and provide a strategy to optimize the effect of CAP cancer treatment.