The inhibitor of histone deacetylases sodium butyrate enhances the cytotoxicity of mitomycin C
Gospodinov, A; Popova, S; Vassileva, I; Anachkova, B
HERO ID
1454734
Reference Type
Journal Article
Year
2012
Language
English
PMID
| HERO ID | 1454734 |
|---|---|
| In Press | No |
| Year | 2012 |
| Title | The inhibitor of histone deacetylases sodium butyrate enhances the cytotoxicity of mitomycin C |
| Authors | Gospodinov, A; Popova, S; Vassileva, I; Anachkova, B |
| Journal | Molecular Cancer Therapeutics |
| Volume | 11 |
| Issue | 10 |
| Page Numbers | 2116-2126 |
| Abstract | The use of histone deacetylase inhibitors has been proposed as a promising approach to increase the cell killing effect of DNA damage-inducing drugs in chemotherapy. However, the molecular mechanism of their action remains understudied. In the present article, we have assessed the effect of the histone deacetylase inhibitor sodium butyrate on the DNA damage response induced by the crosslinking agent mitomycin C. Sodium butyrate increased mitomycin C cytotoxicity, but did not impair the repair pathways required to remove mitomycin C-induced lesions as neither the rate of nucleotide excision repair nor the homologous recombination repair rate were diminished. Sodium butyrate treatment abrogated the S-phase cell-cycle checkpoint in mitomycin C-treated cells and induced the G(2)-M checkpoint. However, sodium butyrate treatment alone resulted in accumulation of reactive oxygen species, double-strand breaks in DNA, and apoptosis. These results imply that the accumulation of reactive oxygen species-mediated increase in DNA lesion burden may be the major mechanism by which sodium butyrate enhances the cytotoxicity of mitomycin C. |
| Doi | 10.1158/1535-7163.MCT-12-0193 |
| Pmid | 22891039 |
| Wosid | WOS:000310638600005 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Source: Web of Science WOS:000310638600005 |
| Is Public | Yes |
| Language Text | English |