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.
Highlights
Radiosensitizers can be beneficial for radiation therapy via increasing cell killing [1]
We have investigated the selective sensitization with suberovlanilide hydroxamic acid (SAHA) treatment in cancer cells versus normal cells
Log growing cells were exposed to different concentrations of SAHA (0.2–4 μM)
Summary
Radiosensitizers can be beneficial for radiation therapy via increasing cell killing [1]. It is important to search clinically approved anti-cancer drugs for novel radiosensitizing effects to avoid complications during drug trials. One pathway identified in these publications was the homologous recombination repair pathway [11,12,13,14], and another pathway was non-homologous end joining repair through Ku70 and 86 [15,16]. These DNA repair inhibitory effects by HDACi were combined with photon ionizing radiation and chemotherapeutic agents, and showed synergistic effects for cell killing. A combination of HDACi with particle radiation, including proton and carbon ion, are still limited [17,18,19,20]
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