Jihye Cha1,2, Tae-Won Jeon1, Chang Geol Lee1, Sang Taek Oh1, Hee-Beom Yang1, Kyung-Ju Choi1, Daekwan Seo3,4, Ina Yun1, In Hye Baik1, Kyung Ran Park5, Young Nyun Park6, Yun-Han Lee1. 1. a Department of Radiation Oncology , Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine , Seoul . 2. b Department of Radiation Oncology , Yonsei University Wonju College of Medicine , Wonju . 3. c Center for RNA Research, Institute for Basic Science, Seoul National University , Seoul . 4. d School of Biological Sciences, Seoul National University , Seoul . 5. e Department of Radiation Oncology , Ewha Womans University Medical Center , Seoul . 6. 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.
Abstract
PURPOSE: 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. MATERIALS AND 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.
PURPOSE: 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. MATERIALS AND METHODS: U87-MG and A172 humanglioma 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 humanglioma 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.
Entities:
Keywords:
Apoptosis; E2F1; cancer stem cells; electro-hyperthermia; glioma
Authors: A L Bredlau; M A McCrackin; Anjan Motamarry; Kris Helke; Chao Chen; Ann-Marie Broome; Dieter Haemmerich Journal: Crit Rev Biomed Eng Date: 2016
Authors: Georgios P Skandalakis; Daniel R Rivera; Caroline D Rizea; Alexandros Bouras; Joe Gerald Jesu Raj; Dominique Bozec; Constantinos G Hadjipanayis Journal: Int J Hyperthermia Date: 2020-07 Impact factor: 3.914