Susceptibility and radiosensitization of human glioblastoma cells to trichostatin A, a histone deacetylase inhibitor.
OBJECTIVE
Histone deacetylase inhibitors (HDAC-Is) show in vitro and in vivo antitumor activity in various types of cancer cells and are being studied in clinical trials. However, studies addressing the combination of HDAC-I and radiation are lacking. The purpose of this study was to assess the effect of trichostatin A (TSA), an HDAC-I, on the radiosensitivity of U373MG and U87MG (human glioblastoma) cell lines.


METHODS
Intrinsic TSA toxicity was determined by measuring survival in exponentially growing cells treated with 0-200 nM TSA for 0-24 h. To assay the radiosensitizing effect of TSA, cells were exposed to 0-200 nM TSA for 18 h before irradiation, and radiation survival curves were obtained. Radiation survival of TSA-treated cells was determined by clonogenic assay.


RESULTS
The human glioblastoma cells showed a dose-dependent reduction in survival and radiosensitization with TSA treatment in the range of 50-200 nM. Exposure to 200 nM TSA resulted in reduced survival of both cell lines, and survival was further reduced with time. Exposure of these cells to TSA before irradiation led to dose-dependent radiosensitization.


CONCLUSIONS
These results suggest that HDAC-Is may be a useful adjunct in the treatment of glioblastoma and merit further investigation. Given the limited efficacy of standard treatments for patients afflicted with glioblastoma, the results reported here provide support for clinical trials integrating HDAC-I with radiation therapy.
Kim
Jin Ho
JH
Department of Therapeutic Radiology, Cancer Research Institute, Seoul National University College of Medicine, 28 Yongon-dong, Jongno-gu, Seoul 110-744, South Korea.
Shin
Jin Hee
JH
Kim
Il Han
IH
D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005909:Glioblastoma / Q000532:radiotherapy*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C012589:trichostatin A