title: Picosecond pulsed electric fields induce apoptosis in HeLa cells via             the endoplasmic reticulum stress and caspase-dependent signaling pathways.
abstract: The non-invasive treatment of tumors with preserved fertility holds great             promise. The application of pulsed electric field (PEF) is a new biomedical engineering             technique for tumor therapy. Picosecond pulsed electric fields (psPEF) can be             transferred to target deep tissue non-invasively and precisely; however, research             of the biological effects of psPEF on cells is limited. Electric theory predicts             that when the pulse duration decreases to nanoseconds and picoseconds, it will             mainly affect organelles and lead to intracellular electromanipulations. Previous             studies have shown that psPEF targets the mitochondria and induces apoptosis through             a mitochondrial-mediated pathway in HeLa cells. The endoplasmic reticulum is also             involved in the intrinsic pathways of apoptosis. In the present study, HeLa cells             were exposed to psPEF to investigate the underlying mechanisms of apoptosis. MTT             assay demonstrated that psPEF displayed strong growth inhibitory effects on HeLa             cells. Treatment with psPEF led to marked cell apoptosis and cell cycle arrest             at the G2/M phase. In addition, psPEF affected the phosphorylation levels of endoplasmic             reticulum 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 elevation             of intracellular Ca2+ concentrations. Furthermore, the activation of caspase-12,             -9 and -3, led to the release of cytochrome c, as well as the upregulation of             Bax 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 HeLa             cells, which exerts its effects, at least partially, via the endoplasmic reticulum             stress and caspase-dependent signaling pathways.
authors: Department of Obstetrics and Gynecology, The Second Affiliated                     Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
authors: Wen-Juan
authors: WJ
authors: Chen
authors: Zheng-Ai
authors: ZA
authors: Xiong
authors: Min
authors: M
authors: Zhang
authors: Chen-Guo
authors: CG
authors: Yao
authors: Zhong-Yong
authors: ZY
authors: Zhao
authors: Yuan-Yuan
authors: YY
authors: Hua
authors: Wei
authors: W
authors: Zhou
mesh_terms: D017209:Apoptosis; D022762:CCAAT-Enhancer-Binding Proteins / Q000096:biosynthesis; D002118:Calcium / Q000378:metabolism; D053454:Caspase 12 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D045304:Cytochromes c / Q000378:metabolism; D015536:Down-Regulation; D004560:Electricity; D004721:Endoplasmic Reticulum / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D004789:Enzyme Activation; D059565:G2 Phase Cell Cycle Checkpoints; D006367:HeLa Cells / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008928:Mitochondria / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D015398:Signal Transduction; D051742:Transcription Factor CHOP / Q000096:biosynthesis; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: C494826:BAX protein, human; D022762:CCAAT-Enhancer-Binding Proteins; C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C053387:endoplasmin; D051742:Transcription Factor CHOP; D045304:Cytochromes c; D053454:Caspase 12; D053148:Caspase 3; D053453:Caspase 9; D002118:Calcium