Histone deacetylase inhibitor induced radiation sensitization effects on human cancer cells after photon and hadron radiation exposure

Ariungerel Gerelchuluun, Junko Maeda, Eri Manabe, Colleen A. Brents, Takeji Sakae, Akira Fujimori, David J. Chen, Koji Tsuboi, Takamitsu A. Kato

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Suberoylanilide hydroxamic acid (SAHA) is a histone deacetylase inhibitor, which has been widely utilized throughout the cancer research field. SAHA-induced radiosensitization in normal human fibroblasts AG1522 and lung carcinoma cells A549 were evaluated with a combination of γ-rays, proton, and carbon ion exposure. Growth delay was observed in both cell lines during SAHA treatment; 2 µM SAHA treatment decreased clonogenicity and induced cell cycle block in G1 phase but 0.2 µM SAHA treatment did not show either of them. Low LET (Linear Energy Transfer) irradiated A549 cells showed radiosensitization effects on cell killing in cycling and G1 phase with 0.2 or 2 µM SAHA pretreatment. In contrast, minimal sensitization was observed in normal human cells after low and high LET radiation exposure. The potentially lethal damage repair was not affected by SAHA treatment. SAHA treatment reduced the rate of γ-H2AX foci disappearance and suppressed RAD51 and RPA (Replication Protein A) focus formation. Suppression of DNA double strand break repair by SAHA did not result in the differences of SAHA-induced radiosensitization between human cancer cells and normal cells. In conclusion, our results suggest SAHA treatment will sensitize cancer cells to low and high LET radiation with minimum effects to normal cells.

Original languageEnglish (US)
Article number496
JournalInternational journal of molecular sciences
Volume19
Issue number2
DOIs
StatePublished - Feb 7 2018

Keywords

  • Carbon ions
  • Proton
  • SAHA

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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  • Cite this

    Gerelchuluun, A., Maeda, J., Manabe, E., Brents, C. A., Sakae, T., Fujimori, A., Chen, D. J., Tsuboi, K., & Kato, T. A. (2018). Histone deacetylase inhibitor induced radiation sensitization effects on human cancer cells after photon and hadron radiation exposure. International journal of molecular sciences, 19(2), [496]. https://doi.org/10.3390/ijms19020496