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


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 G2/M arrest, whereas HDIs abolished the latter.


CONCLUSIONS
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.
Kumar
K Saravana
KS
Research Center of Pharmacology and Experimental Therapeutics, Ernst Moritz Arndt University, Greifswald, Germany.
Sonnemann
Jürgen
J
Hong
Le Thi Thu
le TT
Buurman
Cornelis
C
Adler
Frank
F
Maass
Manfred
M
Völker
Uwe
U
Beck
James F
JF
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D008527:Medulloblastoma / Q000188:drug therapy* / Q000201:enzymology / Q000532:radiotherapy*; D014750:Vincristine / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D014750:Vincristine