Histone deacetylase inhibitors radiosensitize human melanoma cells by suppressing DNA repair activity.

摘要: Purpose: Histone deacetylase (HDAC) inhibitors have emerged recently as promising anticancer agents. They arrest cells in the cell cycle and induce differentiation death. The antitumor activity of HDAC has been linked to their ability gene expression through acetylation histone nonhistone proteins. However, it suggested that may also enhance other cancer therapeutics, including radiotherapy. purpose this study was evaluate radiosensitize human melanoma vitro. Experimental Design: A panel included sodium butyrate (NaB), phenylbutyrate, tributyrin, trichostatin were tested for two lines (A375 MeWo) using clonogenic survival assays. Apoptosis DNA repair measured by standard Results: NaB induced hyperacetylation H4 normal fibroblasts. radiosensitized both A375 MeWo lines, substantially reducing surviving fraction at 2 Gy (SF2), whereas had no effect on inhibitors, significant radiosensitizing effects tested. modestly enhanced radiation-induced apoptosis did not correlate with but functional impairment determined based host reactivation assay. Moreover, significantly reduced repair-related genes Ku70 Ku86 DNA-dependent protein kinase catalytic subunit mRNA levels. Normal fibroblasts showed change capacity or levels proteins following treatment. We examined γ-H2AX phosphorylation a marker radiation response observed compared controls, foci persisted long after ionizing exposure NaB-treated cells. Conclusions: tumor affecting damage can be used predictive radioresponse.