Effects of tetrandrine plus radiation on neuroblastoma cells
Journal
Anticancer Research
Journal Volume
29
Journal Issue
8
Pages
3163-3171
Date Issued
2009
Author(s)
Abstract
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 radio sensitization 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/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.
Subjects
Cytotoxicity; Neuroblastoma; Radiosensitization; Tetrandrine
SDGs
Other Subjects
bisbenzylisoquinoline alkaloid; tetrandrine; article; cancer combination chemotherapy; cancer radiotherapy; cell cycle; cell cycle G0 phase; cell cycle G1 phase; cell cycle G2 phase; cell cycle M phase; controlled study; cytotoxicity; fluorescence activated cell sorting; human; human cell; human tissue; neuroblastoma cell; priority journal; radiation dose; radiosensitization; Antineoplastic Agents, Phytogenic; Benzylisoquinolines; Cell Cycle; Cell Death; Cesium Radioisotopes; Combined Modality Therapy; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Drugs, Chinese Herbal; Humans; Neuroblastoma; Radiation-Sensitizing Agents; Tumor Cells, Cultured; Tumor Stem Cell Assay
Type
journal article