Histone deacetylase inhibitors, but not vincristine, cooperate with radiotherapy to induce cell death in medulloblastoma

作者：Kumar K Saravana; Sonnemann Juergen; Hong Le Thi Thu; Buurman Cornelis; Adler Frank; Maass Manfred; Voelker Uwe; Beck James F^*

来源：Anticancer Research, 2007, 27(1A): 465-470.

• cell cycle
• histone deacetylase inhibitors
• ionising radiation
• medulloblastoma cells
• suberoylanilide hydroxamic acid (SAHA)
• trichostatin A
• vincristine

Background: Though ionising radiation (IR) is an efficient means of postoperative treatment for children with medulloblastoma, the disease is incurable in about a third of them. Thus, multimodality regimens have been introduced, typically combining IR with vincristine. Materials and Methods: The combination of IR and vincristine was compared to the combination of IR and histone deacetylase inhibitors (HDIs) for their anticancer activity against medulloblastoma cells in vitro. Cytotoxic activities were assessed by measuring propidium iodide uptake and by cell cycle analysis. Results: HDIs augmented the cytotoxic effect of IR, while the combination of vincristine and IR was significantly less cytotoxic than vincristine alone. Cell cycle analyses revealed that vincristine did not interfere with IR-induced G(2)/M arrest, whereas HDIs abolished the latter. Conclusion: These in vitro findings indicate a favourable interaction of IR and HDIs, but an unfavourable one of IR and vincristine, in medulloblastoma, and provide a rationale for comparing the combination of IR with either vincristine or HDIs in vivo.

• 出版日期2007-2