A Histone Deacetylase Inhibitor, Trichostatin A, Enhances Radiosensitivity by Abrogating G2/M Arrest in Human Carcinoma Cells.
- Author:
In Ah KIM
1
;
Jin Ho KIM
;
Jin Hee SHIN
;
Il Han KIM
;
Jae Sung KIM
;
Hong Gyun WU
;
Eui Kyu CHIE
;
Yong Ho KIM
;
Bo Kyung KIM
;
Semie HONG
;
Seok Won PARK
;
Sung Whan HA
;
Charn Il PARK
Author Information
1. Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea. ihkim@snu.ac.kr
- Publication Type:Original Article
- Keywords:
Trichostatin A;
Histone deacetylase inhibitor;
Radiosensitization;
G2/M arrest
- MeSH:
Acetylation;
Apoptosis;
Blotting, Western;
Cell Cycle;
Cell Line;
Cell Survival;
Histone Deacetylase Inhibitors*;
Histone Deacetylases*;
Histones*;
Humans*;
Radiation Tolerance*;
Radiation-Sensitizing Agents
- From:Cancer Research and Treatment
2005;37(2):122-128
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: 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. MATERIALS AND 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. CONCLUSION: The pretreatment of TSA enhanced the radiosensitivity of a panel of human carcinoma cells, which was attributed, in part, to the abrogation of radiationinduced G2/M arrest.
