title: Administration of salubrinal enhances radiation-induced cell death of SW1353 chondrosarcoma cells.
abstract: BACKGROUND
  Chondrosarcoma is a common soft tissue malignancy. Although radiation induces DNA damage and integrated stress response (ISR), the sensitivity to ionizing radiation differs among tissues, and traditional radiotherapy for chondrosarcoma is not deemed effective. We examined whether administration of an ISR-inducing agent enhances radiosensitivity of chondrosarcoma.
  
  
  METHODS
  SW1353 chondrosarcoma cells and C28/I2 chondrocytes were irradiated with 1-10 Gy of X-rays and cultured with 1-20 μM salubrinal, which is known to induce ISR through inhibiting dephosphorylation of eukaryotic translation initiation factor 2α (eIF2α).
  
  
  RESULTS
  The numbers of cells were reduced after irradiation, and salubrinal further reduced them as well as their clonogenic survival. The levels of phosphorylated eIF2α were elevated by irradiation and administration of salubrinal. SW1353 cells treated with salubrinal after irradiation were more sensitive to radiation than those treated with salubrinal prior to irradiation.
  
  
  CONCLUSIONS
  Salubrinal may serve as a potential chemotherapeutic agent for enhancing radiosensitivity, and its efficacy may depend upon the dose used and the timing of its administration.
authors.affiliation: Division of Medical Physics, Oncology Center, Osaka University Hospital, Osaka, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Koizumi
authors.forename: Nancy G
authors.initials: NG
authors.lastname: Tanjung
authors.forename: Andy
authors.initials: A
authors.lastname: Chen
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Dynlacht
authors.forename: Joy
authors.initials: J
authors.lastname: Garrett
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yoshioka
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ogawa
authors.forename: Teruki
authors.initials: T
authors.lastname: Teshima
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yokota
mesh_terms: D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002813:Chondrosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D002934:Cinnamates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D015852:Eukaryotic Initiation Factor-2; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000528:radiation effects; D010766:Phosphorylation; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D002934:Cinnamates; D015852:Eukaryotic Initiation Factor-2; D011838:Radiation-Sensitizing Agents; C496827:salubrinal; D013890:Thiourea