title: Biological effect of an alternating electric field on cell proliferation and synergistic antimitotic effect in combination with ionizing radiation.
abstract: Alternating electric fields at an intermediate frequency (100~300 kHz), referred to as tumour-treating fields (TTF), are believed to interrupt the process of mitosis via apoptosis and to act as an inhibitor of cell proliferation. Although the existence of an antimitotic effect of TTF is widely known, the proposed apoptotic mechanism of TTF on cell function and the efficacy of TTF are controversial issues among medical experts. To resolve these controversial issues, a better understanding of the underlying molecular mechanisms of TTF on cell function and the differences between the effects of TTF alone and in combination with other treatment techniques is essential. Here, we report experimental evidence of TTF-induced apoptosis and the synergistic antimitotic effect of TTF in combination with ionizing radiation (IR). For these experiments, two human Glioblastoma multiforme (GBM) cells (U373 and U87) were treated either with TTF alone or with TTF followed by ionizing radiation (IR). Cell apoptosis, DNA damage, and mitotic abnormalities were quantified after the application of TTF, and their percentages were markedly increased when TTF was combined with IR. Our experimental results also suggested that TTF combined with IR synergistically suppressed both cell migration and invasion, based on the inhibition of MMP-9 and vimentin.
authors.affiliation: Korea Institute of Radiological & Medical Sciences, Seoul, 01812, Korea.
authors.forename: Eun Ho
authors.initials: EH
authors.lastname: Kim
authors.affiliation: Korea Institute of Radiological & Medical Sciences, Seoul, 01812, Korea.
authors.forename: Ye Ho
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Bio-Convergence Engineering, Korea University, Seoul, 02841, Korea.
authors.forename: Hyo Sook
authors.initials: HS
authors.lastname: Song
authors.affiliation: Korea Institute of Radiological & Medical Sciences, Seoul, 01812, Korea.
authors.forename: Youn Kyoung
authors.initials: YK
authors.lastname: Jeong
authors.affiliation: Korea Institute of Radiological & Medical Sciences, Seoul, 01812, Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Bio-Convergence Engineering, Korea University, Seoul, 02841, Korea.
authors.forename: Jiwon
authors.initials: J
authors.lastname: Sung
authors.affiliation: Korea Institute of Radiological & Medical Sciences, Seoul, 01812, Korea.
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Yoo
authors.affiliation: Department of Bio-Convergence Engineering, Korea University, Seoul, 02841, Korea.
authors.forename: Myonggeun
authors.initials: M
authors.lastname: Yoon
mesh_terms: D017209:Apoptosis / Q000528:radiation effects*; D001932:Brain Neoplasms / Q000628:therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000528:radiation effects*; D049109:Cell Proliferation / Q000528:radiation effects*; D003131:Combined Modality Therapy / Q000379:methods; D004599:Electric Stimulation Therapy / Q000379:methods*; D005909:Glioblastoma / Q000628:therapy*; D006801:Humans; D007150:Immunohistochemistry; D020780:Matrix Metalloproteinase 9 / Q000528:radiation effects; D008938:Mitosis / Q000528:radiation effects*; D011878:Radiotherapy / Q000379:methods*; D014746:Vimentin / Q000528:radiation effects
chemical_list: D014746:Vimentin; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: apoptosis; glioblastoma multiforme; ionizing radiation; synergism; tumour-treating fields