TY - JOUR T1 - Effects of Tetrandrine plus Radiation on Neuroblastoma Cells JF - Anticancer Research JO - Anticancer Res SP - 3163 LP - 3171 VL - 29 IS - 8 AU - YUN CHEN AU - JIN-CHERNG CHEN AU - SHENG-HONG TSENG Y1 - 2009/08/01 UR - http://ar.iiarjournals.org/content/29/8/3163.abstract N2 - Background: Tetrandrine, a bisbenzylisoquinoline alkaloid, has cancer cell cytotoxicity. The effects of combined tetrandrine and radiation, alone or combined, on human SH-SY5Y 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 G2/M-phase of the cell cycle, while tetrandrine caused G0/G1 accumulation. Compared to RT alone, RT-Tet increased the G0/G1 fraction and decreased the G2/M accumulation (p<0.001), whereas Tet-RT led to no reduction in radiation-induced G2/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 G2/M accumulation. ER -