Sensitivity of human glioma U-373MG cells to radiation and the protein kinase C inhibitor, calphostin C.
We assessed the radiosensitivity of the grade III human glioma cell line U-373MG by investigating the effects of radiation and the specific protein kinase C inhibitor, calphostin C on the cell cycle and cell proliferation. Irradiated glioma U-373MG cells progressed through G1-S and underwent an arrest in G2-M phase. The radiosensitivity of U-373MG cells to graded doses of either photons or electrons was determine by microculture tetrazolium assay. The data was fitted to the linear-quadratic model. The proliferation curves demonstrated that U-373MG cells appear to be highly radiation resistant since 8 Gy was required to achieve 50% cell mortality. Compared to radiation alone, exposure to calphostin C (250 nM) 1 h prior to radiation decreased the proliferation of U-373MG by 76% and calphostin C provoked a weakly synergistic effect in concert with radiation. Depending on the time of application following radiation, calphostin C produced an additive or less than additive effect on cell proliferation. We postulate that the enhanced radiosensitivity observed when cells are exposed to calphostin C prior to radiation may be due to direct or indirect inhibition of protein kinase C isozymes required for cell cycle progression.
Acevedo-Duncan
M
M
James A. Haley Veterans Hospital, and Department of Chemistry, University of South Florida, Tampa 33612, USA. acevedo@chuma.cas.usf.edu
Pearlman
J
J
Zachariah
B
B
D001932:Brain Neoplasms / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005910:Glioma / Q000473:pathology*; D006801:Humans; D009281:Naphthalenes / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011839:Radiation, Ionizing; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D009281:Naphthalenes; D011493:Protein Kinase C; C058819:calphostin C