Association of elevated reactive oxygen species and hyperthermia induced radiosensitivity in cancer stem-like cells

// Qibin Fu 1 , Tuchen Huang 1 , Xudong Wang 2 , Chunyang Lu 2 , Feng Liu 2 , Gen Yang 2 , Yugang Wang 2 and Biao Wang 1 1 Sino-French Institute of Nuclear Engineering and Technology, Sun Yat-sen University, Zhuhai 519082, P. R. China 2 State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing 100871, P. R. China Correspondence to: Gen Yang, email: gen.yang@pku.edu.cn Biao Wang, email: wangbiao@mail.sysu.edu.cn Keywords: cancer stem-like cells, hyperthermia, radiosensitivity, reactive oxygen species Received: June 27, 2017      Accepted: September 21, 2017      Published: October 09, 2017 ABSTRACT Cancer stem-like cells (CSCs) are the principal causes of tumor radio-resistance, dormancy and recurrence after radiotherapy. Clinical trials show hyperthermia (HT) might be a potent radiation sensitizer. In this study, CSCs were found to be more susceptible to radiation when combined with HT treatment. Treated cells showed significantly reduced self-renewal, cell survival and proliferation in vitro , as well as significant reduced tumor formation in vivo . Further study demonstrated that the radiosensitization effect was associated with increased intracellular reactive oxygen species (ROS) level in CSCs, confirmed by modifying redox status in CSCs bidirectionally. Pharmacologic depletion of glutathione by buthionine sulphoximine mimicked HT induced radiosensitivity in CSCs. Antioxidant N-acetylcysteine could efficiently rescue HT induced radiosensitivity in CSCs. To our knowledge, this may be the first report suggesting the association between elevated intracellular ROS level and HT induced radiosensitization in human breast CSCs and pancreatic CSCs, which might provide new strategy for improving CSCs radiosensitivity.