Administration of Salubrinal Enhances Radiation-induced Cell Death of SW1353 Chondrosarcoma Cells

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. 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). 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. 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.