Nanosecond pulsed electric fields have differential effects on cells in the S-phase.
Nanosecond pulsed electric fields (nsPEFs) are a type of nonthermal, nonionizing radiation that exhibit intense electric fields with high power, but low energy. NsPEFs extend conventional electroporation (EP) to affect intracellular structures and functions and depending on the intensity, can induce lethal and nonlethal cell signaling. In this study, HCT116 human colon carcinoma cells were synchronized to the S-phase or remained unsynchronized, exposed to electric fields of 60 kV/cm with either 60-ns or 300-ns durations, and analyzed for apoptosis and proliferative markers. Several nsPEF structural and functional targets were identified. Unlike unsynchronized cells, S-phase cells under limiting conditions exhibited greater membrane integrity and caspase activation and maintained cytoskeletal structure. Regardless of synchronization, cells exposed to nsPEFs under these conditions primarily survived, but exhibited some turnover and delayed proliferation in cell populations, as well as reversible increases in phosphatidylserine externalization, membrane integrity, and nuclei size. These results show that nsPEFs can act as a nonligand agonist to modulate plasma membrane (PM) and intracellular structures and functions, as well as differentially affect cells in the S-phase, but without effect on cell survival. Furthermore, nsPEF effects on the nucleus and cytoskeleton may provide synergistic therapeutic actions with other agents, such as ionizing radiation or chemotherapeutics that affect these same structures.
Hall
Emily H
EH
Center for Pediatric Research, Eastern Virginia Medical School, Children's Hospital of the King's Daughters, Norfolk, Virginia 23510, USA.
Schoenbach
Karl H
KH
Beebe
Stephen J
SJ
D000199:Actins / Q000378:metabolism / Q000528:radiation effects; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation; D002462:Cell Membrane / Q000528:radiation effects; D002467:Cell Nucleus / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects*; D002470:Cell Survival; D003593:Cytoplasm / Q000528:radiation effects; D004560:Electricity; D006801:Humans; D011840:Radiation, Nonionizing; D016196:S Phase / Q000187:drug effects / Q000528:radiation effects*; D013936:Thymidine / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000199:Actins; D020169:Caspases; D013936:Thymidine