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

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.
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.
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 G2/M arrest, whereas HDIs abolished the latter.
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.
AuthorsK Saravana Kumar, Jürgen Sonnemann, Le Thi Thu Hong, Cornelis Buurman, Frank Adler, Manfred Maass, Uwe Völker, James F Beck
JournalAnticancer research (Anticancer Res) 2007 Jan-Feb Vol. 27 Issue 1A Pg. 465-70 ISSN: 0250-7005 [Print] Greece
PMID17352268 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents, Phytogenic
  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Vincristine
  • Antineoplastic Agents, Phytogenic (pharmacology)
  • Cell Death (drug effects, radiation effects)
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Enzyme Inhibitors (pharmacology)
  • Histone Deacetylase Inhibitors
  • Humans
  • Medulloblastoma (drug therapy, enzymology, radiotherapy)
  • Vincristine (antagonists & inhibitors, pharmacology)

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