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Electro-hyperthermia up-regulates tumour suppressor Septin 4 to induce apoptotic cell death in hepatocellular carcinoma

Authors
 Tae-Won Jeon  ;  Heebum Yang  ;  Chang Geol Lee  ;  Sang Taek Oh  ;  Daekwan Seo  ;  In Hye Baik  ;  Eun Hye Lee  ;  Ina Yun  ;  Kyung Ran Park  ;  Yun-Han Lee 
Citation
 INTERNATIONAL JOURNAL OF HYPERTHERMIA, Vol.32(6) : 648-656, 2016 
Journal Title
INTERNATIONAL JOURNAL OF HYPERTHERMIA
ISSN
 0265-6736 
Issue Date
2016
Abstract
PURPOSE: Modulated electro-hyperthermia (mEHT) has been shown to be effective against various types of human tumours, including hepatocellular carcinoma (HCC). Here we aimed to investigate the molecular mechanism underlying the cytotoxic effects of mEHT to HCC cells.

MATERIALS AND METHODS: Human liver cancer cell lines, Huh7 and HepG2, were treated with mEHT (42 °C/60 min) three times at 2-day intervals. Growth inhibition and apoptotic induction were evaluated using MTS, microscopic analysis, a clonogenic assay, annexin V/PI staining and a ccK18 ELISA. Global changes in gene expression were examined using RNA sequencing to obtain insights into molecular changes in response to mEHT. For in vivo evaluation of mEHT we used HepG2 HCC xenografts grown in nude mice.

RESULTS: mEHT suppressed HCC cell proliferation and long-term colony formation through induction of apoptosis. The growth inhibitory effects are induced through a subset of molecular changes. Notably the expression level of septin 4 (SEPT4) (involved in pro-apoptotic activity and growth suppression) was up-regulated, whereas a key regulator of invasiveness G-Protein coupled receptor 64 (GPR64) was repressed. Subsequent Western blotting confirmed that the common increase in tumour suppressor SEPT4 in both Huh7 and HepG2 cells is accompanied by the restoration of cyclin-dependent kinase (CDK) inhibitor p21 and decrease in pro-caspase 7 and pro-caspase 3, thereby accelerating apoptotic signalling in HCC cells. Additionally, mEHT significantly inhibited the growth of human HCC xenografts in nude mice.

CONCLUSIONS: These findings suggest that apoptotic cell death induced by mEHT is mediated by the up-regulation of tumour suppressor SEPT4 in human HCC cells.
Full Text
http://www.tandfonline.com/doi/abs/10.1080/02656736.2016.1186290
DOI
10.1080/02656736.2016.1186290
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Lee, Chang Geol(이창걸) ORCID logo https://orcid.org/0000-0002-8702-881X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/155806
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