title: RAD001 enhances the radiosensitivity of SCC4 oral cancer cells by inducing cell cycle arrest at the G2/M checkpoint.
abstract: BACKGROUND
  Inhibition of mammalian target of rapamycin (mTOR) kinase enhances the radiosensitivity of some cancer cells. We investigated the effect of RAD001, an mTOR inhibitor, on irradiated oral cancer cell lines.
  
  
  METHODS
  Clonogenic assays were performed to determine the radiosensitivity of SCC4 and SCC25 cells after treatment with RAD001. Target protein phosphorylation, apoptosis, and cell-cycle progression were assessed in SCC4 cells treated with RAD001 with and without ionizing radiation.
  
  
  RESULTS
  RAD001 increased the radiosensitivity of SCC4 cells without affecting cell death; it also inhibited phosphorylation of mTOR, S6, and factor 4E binding protein 1 and reduced the clonogenic survival of irradiated cancer cells. RAD001 combined with radiation increased G2 arrest by activating CHK1, which phosphorylates CDC25C at Ser216, thereby inhibiting CDC2-cyclin B 1 complex formation.
  
  
  CONCLUSIONS
  RAD001 enhances the radiosensitivity of SCC4 cells by inhibiting mTOR signaling and inducing G2 cell-cycle arrest through disruption of the G2 checkpoint.
authors.affiliation: Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi, Taiwan, R.O.C. Division of Hematology-Oncology, Department of Internal Medicine, Buddhist Dalin Tzu Chi Hospital, Chia-Yi, Taiwan, R.O.C.
authors.forename: Chih-Chia
authors.initials: CC
authors.lastname: Yu
authors.affiliation: School of Medicine, Tzu Chi University, Hualian, Taiwan, R.O.C. Department of Radiation Oncology, Buddhist Dalin Tzu Chi Hospital, Chia-Yi, Taiwan, R.O.C.
authors.forename: Shih-Kai
authors.initials: SK
authors.lastname: Hung
authors.affiliation: Department of Biochemical Science and Technology, National Chiayi University, Chia-Yi, Taiwan, R.O.C.
authors.forename: Hui-Fen
authors.initials: HF
authors.lastname: Liao
authors.affiliation: School of Medicine, Tzu Chi University, Hualian, Taiwan, R.O.C. Department of Otolaryngology, Buddhist Dalin Tzu Chi Hospital, Chia-Yi, Taiwan, R.O.C.
authors.forename: Ching-Chih
authors.initials: CC
authors.lastname: Lee
authors.affiliation: School of Medicine, Tzu Chi University, Hualian, Taiwan, R.O.C. Department of Radiation Oncology, Buddhist Dalin Tzu Chi Hospital, Chia-Yi, Taiwan, R.O.C.
authors.forename: Hon-Yi
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Buddhist Dalin Tzu Chi Hospital, Chia-Yi, Taiwan, R.O.C.
authors.forename: Hung-Chih
authors.initials: HC
authors.lastname: Lai
authors.affiliation: Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi, Taiwan, R.O.C. Division of Hematology-Oncology, Department of Internal Medicine, Buddhist Dalin Tzu Chi Hospital, Chia-Yi, Taiwan, R.O.C.
authors.forename: Szu-Chin
authors.initials: SC
authors.lastname: Li
authors.affiliation: School of Medicine, Tzu Chi University, Hualian, Taiwan, R.O.C. Department of Otolaryngology, Buddhist Dalin Tzu Chi Hospital, Chia-Yi, Taiwan, R.O.C.
authors.forename: Hsu-Chueh
authors.initials: HC
authors.lastname: Ho
authors.affiliation: Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi, Taiwan, R.O.C. biohbh@ccu.edu.tw hepatoma@gmail.com.
authors.forename: Hsien-Bin
authors.initials: HB
authors.lastname: Huang
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Buddhist Dalin Tzu Chi Hospital, Chia-Yi, Taiwan, R.O.C. School of Medicine, Tzu Chi University, Hualian, Taiwan, R.O.C. biohbh@ccu.edu.tw hepatoma@gmail.com.
authors.forename: Yu-Chieh
authors.initials: YC
authors.lastname: Su
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D002453:Cell Cycle / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D000068338:Everolimus; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011836:Radiation Tolerance / Q000187:drug effects*; D011839:Radiation, Ionizing; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D014062:Tongue Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D014407:Tumor Cells, Cultured
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: G2 checkpoint; SCC4 cells; mTOR; radiosensitization