Trichostatin A, a Histone Deacetylase Inhibitor, Potentiated Cytotoxic Effect of Ionizing Radiation in Human Head and Neck Cancer Cell Lines

Kim,  Jin Ho; Shin,  Jin Hee; Chie,  Eui Kyu; Wu,  Hong Gyun; Kim,  Jae Sung; Kim,  Il Han; Ha,  Sung Whan; Park,  Charn Il; Kang,  Wee Saing

J Korean Soc Ther Radiol Oncol > Volume 22(2); 2004 > Article

Original Article

The Journal of the Korean Society for Therapeutic Radiology and Oncology 2004;22(2): 138-144.

Trichostatin A, a Histone Deacetylase Inhibitor, Potentiated Cytotoxic Effect of Ionizing Radiation in Human Head and Neck Cancer Cell Lines

Jin Ho Kim, Jin Hee Shin, Eui Kyu Chie, Hong Gyun Wu, Jae Sung Kim, Il Han Kim, Sung Whan Ha, Charn Il Park, Wee Saing Kang

¹Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea. ihkim@snu.ac.kr
²Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
³Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.

ABSTRACT

PURPOSE:
We have previously reported that human glioblastoma cells are sensitized to radiation-induced death after their exposure to trichostatin A (TSA), a histone deacetylase inhibitor (HDAC-I), prior to the irradiation. We aimed to measure the magnitude of the radiosensitizing effect of TSA in human head and neck cancer cell lines. MATERIALS AND MEHTODS: Human head and neck cancer cell lines, HN-3 and HN-9, were exposed to 0, 50, 100, and 200 nM TSA for 18 hr prior to irradiation. Then, the TSA-treated cells were irradiated with 0, 2, 4, 6, and 8 Gy, and cell survival was measured by clonogenic assay.
RESULTS:
Pre-irradiation exposure to TSA was found to radiosensitize HN-3 and HN-9 cell lines. In HN-9 cells, the fraction surviving after 2 Gy (SF2) was significantly reduced by treatment of TSA at concentration as low as 50 nM. However, a treatment with 200 nM TSA was required to significantly decrease SF2 in the HN-3 cell line. SER of pre-irradiation treatment with 200 nM TSA was 1.84 in HN-3 and 7.24 in HN-9, respectively.
CONCLUSIONS:
Our results clearly showed that human head and neck cancer cell lines can be sensitized to ionizing radiation by pre-irradiation inhibition of histone deacetylase (HDAC) using TSA, and that this potentiation might well be a general phenomenon.

Key Words: Trichostatin A, Histone deacetylase inhibitor, Radiosensitization, Head and neck cancer