Electrostimulation\nEvokes Caspase-3-Activated Fast\nCancer Cell Pyroptosis and Its Nuclear Stress Response Pathways

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