American Association for Cancer Research
15417786mcr110587-sup-data_3_152k.pdf (152.75 kB)

Supplementary Data 3 from Suberoylanilide Hydroxamic Acid as a Radiosensitizer through Modulation of RAD51 Protein and Inhibition of Homology-Directed Repair in Multiple Myeloma

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journal contribution
posted on 2023-04-03, 17:43 authored by Xufeng Chen, Patty Wong, Eric H. Radany, Jeremy M. Stark, Corentin Laulier, Jeffrey Y.C. Wong

PDF file - 152K, (A) Western blotting assay; (B) Densitometry for changes of gamma-H2AX. MM cells were treated with or without 200 nM of SAHA for 16 hours, followed by 6 Gy IR. Whole cell extracts were prepared at indicated time points after IR, and analyzed by western blot assay with anti-gamma-H2AX antibody. Anti-tubulin antibody was included as a loading control



Histone deacetylase inhibitors (HDI) have shown promise as candidate radiosensitizers for many types of cancers. However, the mechanisms of action are not well understood, and whether they could sensitize multiple myeloma (MM) to radiation therapy is unclear. In this study, we show that suberoylanilide hydroxamic acid (SAHA) at low concentrations has minimal cytotoxic effects, yet can significantly increase radiosensitivity of MM cells. SAHA seems to block RAD51 protein response to ionizing radiation, consistent with an inhibitory effect on the formation of RAD51 focus in irradiated MM cells. These effects of SAHA on RAD51 focus are independent of cell-cycle distribution changes. Furthermore, we show that SAHA selectively inhibits the homology-directed repair (HDR) pathway. The results of this study suggest that SAHA, a recently approved HDI in clinical trials for malignancies, at lower concentrations may act as a radiosensitizer via disruption of the RAD51-dependent HDR pathway. Mol Cancer Res; 10(8); 1052–64. ©2012 AACR.