Abstract:Purpose/Objective: Histone deacetylase inhibitors (HDACI) show in vitro and in vivo anti-tumor activity for a variety of types of cancer cells and are being studied in clinical trials. But studies addressing the combination with radiation are lacking. The purpose of this study is to assess the effect of trichostatin A (TSA), a HDACI, on the radiosensitivity of human glioblastoma cells. Materials/Methods: To evaluate the effect of combination of TSA and radiation, exponentially growing U373MG and U87MG cells were exposed to TSA for 18 hours before irradiation, and radiation survival was measured by clonogenic assay. The effect of TSA on the cell cycle and apoptosis induction was analyzed by the flow cytometry. Results: Pre-irradiation exposure to TSA significantly radiosensitized U373MG and U87MG cells at 2 Gy. This effect of TSA was concentration-dependent, but 200 nM TSA was associated with significant direct cytotoxicity as well as radiosensitization with sensitizer enhancement ratio of 1.4 to 1.5. Exposure to 50-100 nM TSA induced significant radiosensitization comparable with that of 200 nM TSA, but revealed virtually no cytotoxicity. Flow cytometry analysis of asynchronous cells exposed to TSA showed the arrest of cell cycle at the G2/M phases and the G1/S transit. TSA induced apoptosis of glioblastoma cells in a concentration- and time-dependent manner. Conclusions: This study firstly demonstrated that TSA sensitized human glioblastoma cells to radiation-induced cell killing at as low concentrations as not to cause direct cytotoxicity. Considering ongoing clinical trials using HDACIs, further study addressing the combination of other HDACIs and radiation is warranted.
Kim MSc, J,
Trichostatin A: A Histone Deacetylase Inhibitor Enhances the Radio-sensitivity of Human Glioblastoma Cells. Radiological Society of North America 2003 Scientific Assembly and Annual Meeting, November 30 - December 5, 2003 ,Chicago IL.
http://archive.rsna.org/2003/3240735.html
