A histone deacetylase inhibitor, trichostatin A, enhances radiosensitivity by abrogating G2/M arrest in human carcinoma cells.
OBJECTIVE
Histone deacetylase inhibitors (HDIs) are emerging as potentially useful components in anticancer therapy. In this study, we tried to confirm the radiosensitizing effect of trichostatin A (TSA) on a panel of human carcinoma cell lines and elucidate its mechanism of interaction.


METHODS
A549, HeLa and Caski cells were exposed to TSA for 18 hr prior to irradiation, and the cell survival then measured using a clonogenic assay. Western blot and flow cytometric analyses, for histone acetylation, and cell cycle and apoptosis, respectively, were also performed.


RESULTS
TSA increased the acetylation of histone H3. The pretreatment of TSA consistently radiosensitized all three cell lines. The SF2 (surviving fraction at 2 Gy) of TSA-treated cells was significantly lower than that of mock treated cells. The SER (sensitizer enhancement ratio) increased in all 3 cell lines, in concentration dependent manners. The TSA treated cells showed abrogation of radiation-induced G2/M arrest, in a concentration dependent manner.


CONCLUSIONS
The pretreatment of TSA enhanced the radiosensitivity of a panel of human carcinoma cells, which was attributed, in part, to the abrogation of radiation-induced G2/M arrest.
Kim
In Ah
IA
Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea.
Kim
Jin Ho
JH
Shin
Jin Hee
JH
Kim
Il Han
IH
Kim
Jae Sung
JS
Wu
Hong-Gyun
HG
Chie
Eui Kyu
EK
Kim
Yong Ho
YH
Kim
Bo-Kyung
BK
Hong
Semie
S
Park
Seok Won
SW
Ha
Sung Whan
SW
Park
Charn Il
CI