HDAC inhibitor sodium butyrate sensitizes E1A+Ras-transformed cells to DNA damaging agents by facilitating formation and persistence of γH2AX foci

Abramova, Maria V.; Svetlikova, S. B.; Кукушкин, А. Н.; Aksenov, N. D.; Поспелова, Т. В.; Поспелов, В. А.

doi:10.4161/cbt.12.12.18365

Cited by 8 publications

(1 citation statement)

References 43 publications

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“…However, further treatment with NaBut led to the persistence of foci for up to 18 h only in transformed cells, but not in non-transformed NIH3T3 cells. We have previously shown that the HDACi sodium butyrate also enhances the accumulation of irradiation-induced γH2AX foci as well as their prolonged persistence [ 39 ].…”

Section: Resultsmentioning

confidence: 99%

HDAC Inhibitor Sodium Butyrate Attenuates the DNA Repair in Transformed but Not in Normal Fibroblasts

Gnedina

Morshneva

Skvortsova

et al. 2022

IJMS

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Many cancer therapy strategies cause DNA damage leading to the death of tumor cells. The DNA damage response (DDR) modulators are considered as promising candidates for use in combination therapy to enhance the efficacy of DNA-damage-mediated cancer treatment. The inhibitors of histone deacetylases (HDACis) exhibit selective antiproliferative effects against transformed and tumor cells and could enhance tumor cell sensitivity to genotoxic agents, which is partly attributed to their ability to interfere with DDR. Using the comet assay and host-cell reactivation of transcription, as well as ɣH2AX staining, we have shown that sodium butyrate inhibited DNA double-strand break (DSB) repair of both endo- and exogenous DNA in transformed but not in normal cells. According to our data, the dysregulation of the key repair proteins, especially the phosphorylated Mre11 pool decrease, is the cause of DNA repair impairment in transformed cells. The inability of HDACis to obstruct DSB repair in normal cells shown in this work demonstrates the advantages of HDACis in combination therapy with genotoxic agents to selectively enhance their cytotoxic activity in cancer cells.

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Section: Resultsmentioning

confidence: 99%