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-SY5Y neuroblastoma cells were examined.


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.


CONCLUSIONS
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.
Chen
Yun
Y
Department of Surgery, Far Eastern Memorial Hospital, Pan-Chiao, Taipei 220, Taiwan R.O.C.
Chen
Jin-Cherng
JC
Tseng
Sheng-Hong
SH
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D044182:Benzylisoquinolines / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D002588:Cesium Radioisotopes; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006801:Humans; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D000972:Antineoplastic Agents, Phytogenic; D044182:Benzylisoquinolines; D002588:Cesium Radioisotopes; D004365:Drugs, Chinese Herbal; D011838:Radiation-Sensitizing Agents; C009438:tetrandrine