Electrostimulation Evokes Caspase-3-Activated Fast Cancer Cell Pyroptosis and Its Nuclear Stress Response Pathways

• Published in: Analytical chemistry (Washington) Vol. 96; no. 33; pp. 13438 - 13446
• Main Authors: Kong, Jiao, Zhang, Ying, Ju, Xingkai, Wang, Bo, Diao, Xingkang, Li, Jing, Qi, Guohua, Jin, Yongdong
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 20.08.2024
• Subjects: Apoptosis; Cancer; Cancer therapies; Caspase 3 - metabolism; Caspase-3; Cell death; Cell Line, Tumor; Cell Nucleus - metabolism; Cellular stress response; Effectiveness; Gasdermins; Humans; Nuclear Proteins - metabolism; Nucleoli; Nucleolin; Nucleophosmin; Nucleoproteins; Phosphate-Binding Proteins - metabolism; Pyroptosis; RNA-Binding Proteins - metabolism
• ISSN: 0003-2700; 1520-6882; 1520-6882
• DOI: 10.1021/acs.analchem.4c01206

Pyroptosis of programmed cell death has been recognized as a more effective way to inhibit the occurrence and development of tumors than the better-studied apoptosis. However, it is still challenging to quickly and effectively trigger pyroptosis of cancer cells for high-efficacy cancer treatment. Here, we report on the first use of mild constant-potential electrostimulation (cp-ES) to quickly trigger cancer cell pyroptosis with a probability up to ∼91.4% and significantly shortened time (within 1 h), ∼3–6 times faster than typical drug stimulation to induce pyroptosis. We find that the ES-induced cancer cell pyroptosis is through the activated caspase-3 (pathway) cleavage of gasdermin E (GSDME) to form an N-terminal fragment (GSDME-N) and observe nuclear shrinkage and reduction of the number of nucleoli as well as down-/up-regulated expression of two important nucleoproteins of nucleolin and nucleophosmin (NPM1). The study enriches the basic understanding of pyroptosis and provides a new avenue for potential effective treatment of cancer.