title: Electro-hyperthermia inhibits glioma tumorigenicity through the induction of E2F1-mediated apoptosis.
abstract: OBJECTIVE
  Modulated electro-hyperthermia (mEHT), also known as oncothermia, shows remarkable treatment efficacies for various types of tumours, including glioma. The aim of the present study was to investigate the molecular mechanism underlying phenotypic changes in oncothermic cancer cells.
  
  
  METHODS
  U87-MG and A172 human glioma cells were exposed to mEHT (42 °C/60 min) three times with a 2-day interval and subsequently tested for growth inhibition using MTS, FACS and microscopic analysis. To obtain insights into the molecular changes in response to mEHT, global changes in gene expression were examined using RNA sequencing. For in vivo evaluation of mEHT, we used U87-MG glioma xenografts grown in nude mice.
  
  
  RESULTS
  mEHT inhibited glioma cell growth through the strong induction of apoptosis. The transcriptomic analysis of differential gene expression under mEHT showed that the anti-proliferative effects were induced through a subset of molecular alterations, including the up-regulation of E2F1 and CPSF2 and the down-regulation of ADAR and PSAT1. Subsequent Western blotting revealed that mEHT increased the levels of E2F1 and p53 and decreased the level of PARP-1, accelerating apoptotic signalling in glioma cells. mEHT significantly suppressed the growth of human glioma xenografts in nude mice. We also observed that mEHT dramatically reduced the portion of CD133(+) glioma stem cell population and suppressed cancer cell migration and sphere formation.
  
  
  CONCLUSIONS
  These findings suggest that mEHT suppresses glioma cell proliferation and mobility through the induction of E2F1-mediated apoptosis and might be an effective treatment for eradicating brain tumours.
authors.affiliation: a Department of Radiation Oncology , Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine , Seoul .|b Department of Radiation Oncology , Yonsei University Wonju College of Medicine , Wonju .
authors.forename: Jihye
authors.initials: J
authors.lastname: Cha
authors.affiliation: a Department of Radiation Oncology , Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine , Seoul .
authors.forename: Tae-Won
authors.initials: TW
authors.lastname: Jeon
authors.affiliation: a Department of Radiation Oncology , Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine , Seoul .
authors.forename: Chang Geol
authors.initials: CG
authors.lastname: Lee
authors.affiliation: a Department of Radiation Oncology , Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine , Seoul .
authors.forename: Sang Taek
authors.initials: ST
authors.lastname: Oh
authors.affiliation: a Department of Radiation Oncology , Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine , Seoul .
authors.forename: Hee-Beom
authors.initials: HB
authors.lastname: Yang
authors.affiliation: a Department of Radiation Oncology , Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine , Seoul .
authors.forename: Kyung-Ju
authors.initials: KJ
authors.lastname: Choi
authors.affiliation: c Center for RNA Research, Institute for Basic Science, Seoul National University , Seoul .|d School of Biological Sciences, Seoul National University , Seoul .
authors.forename: Daekwan
authors.initials: D
authors.lastname: Seo
authors.affiliation: a Department of Radiation Oncology , Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine , Seoul .
authors.forename: Ina
authors.initials: I
authors.lastname: Yun
authors.affiliation: a Department of Radiation Oncology , Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine , Seoul .
authors.forename: In Hye
authors.initials: IH
authors.lastname: Baik
authors.affiliation: e Department of Radiation Oncology , Ewha Womans University Medical Center , Seoul .
authors.forename: Kyung Ran
authors.initials: KR
authors.lastname: Park
authors.affiliation: f Department of Pathology , Brain Korea 21 PLUS Project for Medical Science, and Severance Biomedical Science Institute, Yonsei University College of Medicine , Seoul , South Korea.
authors.forename: Young Nyun
authors.initials: YN
authors.lastname: Park
authors.affiliation: a Department of Radiation Oncology , Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine , Seoul .
authors.forename: Yun-Han
authors.initials: YH
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy*; D050687:E2F1 Transcription Factor / Q000502:physiology*; D004599:Electric Stimulation Therapy; D005434:Flow Cytometry; D005910:Glioma / Q000473:pathology / Q000628:therapy*; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D051379:Mice; D008819:Mice, Nude
chemical_list: D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human
keywords: Apoptosis; E2F1; cancer stem cells; electro-hyperthermia; glioma