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The non-invasive treatment of tumors with preserved fertility holds greatpromise. The application of pulsed electric field (PEF) is a new biomedical engineeringtechnique for tumor therapy. Picosecond pulsed electric fields (psPEF) can betransferred to target deep tissue non-invasively and precisely; however, researchof the biological effects of psPEF on cells is limited. Electric theory predictsthat when the pulse duration decreases to nanoseconds and picoseconds, it willmainly affect organelles and lead to intracellular electromanipulations. Previousstudies have shown that psPEF targets the mitochondria and induces apoptosis througha mitochondrial-mediated pathway in HeLa cells. The endoplasmic reticulum is alsoinvolved in the intrinsic pathways of apoptosis. In the present study, HeLa cellswere exposed to psPEF to investigate the underlying mechanisms of apoptosis. MTTassay demonstrated that psPEF displayed strong growth inhibitory effects on HeLacells. Treatment with psPEF led to marked cell apoptosis and cell cycle arrestat the G2/M phase. In addition, psPEF affected the phosphorylation levels of endoplasmicreticulum sensors and upregulated the expression of glucose-regulated protein 78(GRP78), glucose-regulated protein 94 (GRP94) and CCAAT enhancer-binding protein(C/EBP) homologous protein (CHOP). These changes were accompanied by the elevationof intracellular Ca2+ concentrations. Furthermore, the activation of caspase-12,-9 and -3, led to the release of cytochrome c, as well as the upregulation ofBax and the downregulation of Bcl-2, as observed in the HeLa cells. Taken together,these data suggest that psPEF is an efficient apoptosis-inducing agent for HeLacells, which exerts its effects, at least partially, via the endoplasmic reticulumstress and caspase-dependent signaling pathways.

Picosecond pulsed electric fields induce apoptosis in HeLa cells via the endoplasmic reticulum stress and caspase-dependent signaling pathways