title: Radiosensitization of human glioma cells by tamoxifen is associated with the inhibition of PKC-ι activityin vitro.
abstract: The present study aimed to investigate the radiosensitizing effects of tamoxifen (TAM), a non-steroidal anti-estrogen drug, in human glioma A172 and U251 cellsin vitro. A colony-forming assay revealed that TAM enhances radiosensitivity in A172 and U251 cells. Treatment with TAM also increased the percentage of apoptotic cells subsequent to ionizing radiation, and increased the expression of apoptotic markers, including cleaved caspase-3 and poly(ADP-ribose) polymerase. Ionizing radiation induced G2/M phase arrest, which was alleviated within 24 h when the radiation-induced DNA damage was repaired. However, flow cytometry analysis revealed that TAM treatment delayed the recovery of cell cycle progression. Additional examination demonstrated that TAM-mediated protein kinase C-ι (PKC-ι) inhibition may lead to the activation of pro-apoptotic B-cell lymphoma 2-associated death promoter, and the dephosphorylation of cyclin-dependent kinase 7, resulting in increased cell apoptosis and sustained G2/M phase arrest following exposure to radiation. The present data indicate that the radiosensitizing effects of TAM on glioma cells are partly due to the inhibition of PKC-ι activityin vitro.
authors.affiliation: Department of Radiobiology, School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences, Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou 215123, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Radiobiology, School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences, Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou 215123, P.R. China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Radiobiology, School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences, Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou 215123, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Radiobiology, School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences, Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou 215123, P.R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Gu
authors.affiliation: Department of Radiobiology, School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences, Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou 215123, P.R. China.
authors.forename: Haowen
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Radiobiology, School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences, Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou 215123, P.R. China.
authors.forename: Jiahua
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Radiobiology, School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences, Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou 215123, P.R. China.
authors.forename: Fenju
authors.initials: F
authors.lastname: Liu
keywords: Bad; cyclin-dependent kinase 7; glioma; protein kinase C-ι; radiosensitivity; tamoxifen