Electrostimulation Evokes Caspase-3-Activated Fast Cancer Cell Pyroptosis and Its Nuclear Stress Response Pathways
Jiao Kong, Ying Zhang, Xingkai Ju, Bo Wang, Xingkang Diao, Jing Li, Guohua Qi, Yongdong Jin
Abstract
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.