| Title: |
HDAC Inhibitor Sodium Butyrate Attenuates the DNA Repair in Transformed but Not in Normal Fibroblasts |
| Authors: |
Olga O. Gnedina; Alisa V. Morshneva; Elena V. Skvortsova; Maria V. Igotti |
| Source: |
International Journal of Molecular Sciences, Vol 23, Iss 3517, p 3517 (2022) |
| Publisher Information: |
MDPI AG |
| Publication Year: |
2022 |
| Collection: |
Directory of Open Access Journals: DOAJ Articles |
| Subject Terms: |
DNA damage response; DSB repair; histone deacetylase inhibitor (HDACi); cancer; MRN complex; Biology (General); QH301-705.5; Chemistry; QD1-999 |
| Description: |
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 γH2AX 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://www.mdpi.com/1422-0067/23/7/3517; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067; https://doaj.org/article/311b9a1f36dc41b78fc54f0737067cd2 |
| DOI: |
10.3390/ijms23073517 |
| Availability: |
https://doi.org/10.3390/ijms23073517; https://doaj.org/article/311b9a1f36dc41b78fc54f0737067cd2 |
| Accession Number: |
edsbas.15174AA1 |
| Database: |
BASE |