Effects of Tetrandrine Plus Radiation on Neuroblastoma Cells

Abstract

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<0.001), whereas Tet-RT led to no reduction in radiation-induced G(2)/M accumulation . Conclusion: Tetrandrine radiosensitization is sequence dependent, with stronger cytotoxic effects noted when radiation is delivered at the beginning of tetrandrine treatment. The effect is, at least partly, related to the partial abrogation of radiation-induced (G(2)/M accumulation .