Mechanisms of Nanosecond Pulsed Electric Field (NsPEF)-Induced Cell Death in Cells and Tumors

The evolution of pulse power technology from high power physics to biology and medicine places nanosecond pulsed electric fields (nsPEFs) in positions for in vitro and in vivo applications as non-ligand agonists that not only bypass plasma membrane receptors for induction of intracellular signaling pathways, but also bypass intracellular oncogenic impasses to induce cell death by regulated mechanisms. Based on work reviewed here, a likely scenario for cell and tumor demise includes nsPEF-induced permeabilization of the plasma membrane, Ca 2+ influx, dissipation of the mitochondrial membrane potential, which is likely due to events beyond permeabilization of the inner mitochondrial membrane, cytochrome c release and activation of caspase-dependent and -independent cell death mechanisms. in vivo , nsPEF-treated orthotopic rat N1-S1 hepatocellular carcinoma tumors exhibit caspase-9 and caspase-3 positive and -negative tumor cells, indicating intrinsic apoptotic and non-apoptotic cell death. Interestingly, after N1-S1 tumor ablation and clearance, rats are resistant to challenge injections of the same N1-S1 tumor cells, indicating a protective, vaccine-like effect that appears to be due to innate and/or adaptive immune responses that are under further investigation. This provides additional impetus to further develop nsPEF ablation as a cancer therapy.