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Electro-hyperthermia inhibits glioma tumorigenicity through the induction of E2F1-mediated apoptosis

Authors
 Jihye Cha  ;  Tae-Won Jeon  ;  Chang Geol Lee  ;  Sang Taek Oh  ;  Hee-Beom Yang  ;  Kyung-Ju Choi  ;  Daekwan Seo  ;  Ina Yun  ;  In Hye Baik  ;  Kyung Ran Park  ;  Young Nyun Park  ;  Yun-Han Lee 
Citation
 INTERNATIONAL JOURNAL OF HYPERTHERMIA, Vol.31(7) : 784-792, 2015 
Journal Title
INTERNATIONAL JOURNAL OF HYPERTHERMIA
ISSN
 0265-6736 
Issue Date
2015
Keywords
electro-hyperthermia ; glioma ; E2F1 ; apoptosis ; cancer stem cells
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.
Full Text
http://www.tandfonline.com/doi/full/10.3109/02656736.2015.1069411
DOI
10.3109/02656736.2015.1069411
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Park, Young Nyun(박영년) ORCID logo https://orcid.org/0000-0003-0357-7967
Baik, In Hye(백인혜)
Lee, Yun Han(이윤한)
Lee, Chang Geol(이창걸) ORCID logo https://orcid.org/0000-0002-8702-881X
Cha, Ji Hye(차지혜)
Choi, Kyung Ju(최경주)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/141576
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