In vitro comparison of conventional hyperthermia and modulated electro-hyperthermia

// Kai-Lin Yang 1, 2, 3 , Cheng-Chung Huang 1 , Mau-Shin Chi 1 , Hsin-Chien Chiang 1 , Yu-Shan Wang 1 , Chien-Chung Hsia 4 , Gabor Andocs 5 , Hsin-Ell Wang 2 , Kwan-Hwa Chi 1, 2, 6 1 Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan 2 Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan 3 School of Medicine, Fu Jen Catholic University, New Taipei, Taiwan 4 Institute of Nuclear Energy Research, Taoyuan, Taiwan 5 Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan 6 Institute of Veterinary Clinical Science, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan Correspondence to: Kwan-Hwa Chi, email: M006565@ms.skh.org.tw Hsin-Ell Wang, email: hewang@ym.edu.tw Keywords: modulated electro-hyperthermia, conventional capacitive coupling hyperthermia, water bath, cytotoxicity, cell membrane Received: May 03, 2016 Accepted: August 11, 2016 Published: August 20, 2016 ABSTRACT Radiofrequency-induced hyperthermia (HT) treatments for cancer include conventional capacitive coupling hyperthermia (cCHT) and modulated electro-hyperthermia (mEHT). In this study, we directly compared these methods with regard to in vitro cytotoxicity and mechanisms of action under isothermal conditions. Hepatoma (HepG2) cells were exposed to HT treatment (42°C for 30 min) using mEHT, cCHT or a water bath. mEHT produced a much higher apoptosis rate (43.1% ± 5.8%) than cCHT (10.0% ± 0.6%), the water bath (8.4% ± 1.7%) or a 37°C control (6.6% ± 1.1%). The apoptosis-inducing effect of mEHT at 42°C was similar to that achieved with a water bath at 46°C. mEHT also increased expression of caspase-3, 8 and 9. All three hyperthermia methods increased intracellular heat shock protein 70 (Hsp70) levels, but only mEHT greatly increased the release of Hsp70 from cells. Calreticulin and E-cadherin levels in the cell membrane also increased after mEHT treatment, but not after cCHT or water bath. These results suggest that mEHT selectively deposits energy on the cell membrane and may be a useful treatment modality that targets cancer cell membranes.