Effects of Tetrandrine Plus Radiation on Neuroblastoma Cells

Background: Tetrandrine, a bisbenzylisoquinoline alkaloid, has cancer cell cytotoxicity. The effects of combined tetrandrine and radiation, alone or combined, on human SH-SY 5Y neuroblastoma cells were examined. Materials and Methods: A combination treatment, using either concomitant irradiation at the beginning or end of the tetrandrine treatment designated as the RT-Tet and Tet-RT protocols, respectively), was used to investigate radiosensitization by tetrandrine. The level of radiosensitization was evaluated by the dose-enhancement ratio and isobologram analysis. The cell cycle distribution of the neuroblastoma cells was examined using flow-activated cell sorter (FACS) analysis. Results: Tetrandrine had a time- and concentration-dependent cytotoxic effect (p<0.05). The dose-enhancement ratio for RT-Tet and Tet-RT was increased, and higher for RT-Tet. Isobologram analysis revealed mainly synergistic cytotoxicity for RT-Tet, but only subadditive cytotoxicity for Tet-RT. FACS analysis revealed that radiation caused accumulation in the G(2)/M-phase of the cell cycle, while tetrandrine caused G(0)/G(1) accumulation. Compared to RT alone, RT-Tet increased the G(0)/G(1), fraction and decreased the G(2)/M accumulation (p