PMID- 25592494 OWN - NLM STAT- MEDLINE DCOM- 20160129 LR - 20190816 IS - 1471-2091 (Electronic) IS - 1471-2091 (Linking) VI - 16 DP - 2015 Jan 16 TI - Histone deacetylase inhibitor sodium butyrate suppresses DNA double strand break repair induced by etoposide more effectively in MCF-7 cells than in HEK293 cells. PG - 2 LID - 10.1186/s12858-014-0030-5 [doi] LID - 2 AB - BACKGROUND: Histone deacetylase inhibitors (HDACi's) are emerging as promising anticancer drugs alone or in combination with chemotherapy or radiotherapy agents. Previous research suggests that HDACi's have a high degree of selectivity for killing cancer cells, but little is known regarding the impact of different cellular contexts on HDACi treatment. It is likely that the molecular mechanisms of HDACi's involve processes that depend on the chromatin template, such as DNA damage and repair. We sought to establish the connection between the HDACi sodium butyrate and DNA double-strand break (DSB) damage in human breast cancer MCF-7 and non-cancerous human embryonic kidney293 (HEK293) cells. RESULTS: Sodium butyrate inhibited the proliferation of both HEK293 and MCF-7 cells in a dose- and time- dependent manner, but the effects on MCF-7 cells were more obvious. This differential effect on cell growth was not explained by differences in cell cycle arrest, as sodium butyrate caused an arrest in G1/G2 phase and a decrease in S phase for both cell lines. At high doses of sodium butyrate or in combination with etoposide, MCF-7 cells formed fewer colonies than HEK293 cells. Furthermore, sodium butyrate enhanced the formation of etoposide-induced gamma-H2AX foci to a greater extent in MCF-7 than in HEK293 cells. The two cells also displayed differential patterns in the nuclear expression of DNA DSB repair proteins, which could, in part, explain the cytotoxic effects of sodium butyrate. CONCLUSIONS: These studies suggest that sodium butyrate treatment leads to a different degree of chromatin relaxation in HEK293 and cancerous MCF-7 cells, which results in differential sensitivity to the toxic effects of etoposide in controlling damaged DNA repair. FAU - Li, Liping AU - Li L AD - Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical College, Xincheng Road, Dongguan, 523808, P R China. lipinggdmc@126.com. AD - Department of Biochemistry, School of Basic Medicine, Guangdong Medical College, Dongguan, 523808, P R China. lipinggdmc@126.com. FAU - Sun, Youxiang AU - Sun Y AD - Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical College, Xincheng Road, Dongguan, 523808, P R China. sunyouxang@aliyun.com. AD - Department of Biochemistry, School of Basic Medicine, Guangdong Medical College, Dongguan, 523808, P R China. sunyouxang@aliyun.com. FAU - Liu, Jiangqin AU - Liu J AD - Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical College, Xincheng Road, Dongguan, 523808, P R China. qliuj@yahoo.com. FAU - Wu, Xiaodan AU - Wu X AD - Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical College, Xincheng Road, Dongguan, 523808, P R China. 843348164@qq.com. AD - Department of Biochemistry, School of Basic Medicine, Guangdong Medical College, Dongguan, 523808, P R China. 843348164@qq.com. FAU - Chen, Lijun AU - Chen L AD - Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical College, Xincheng Road, Dongguan, 523808, P R China. 573394815@qq.com. AD - Department of Biochemistry, School of Basic Medicine, Guangdong Medical College, Dongguan, 523808, P R China. 573394815@qq.com. FAU - Ma, Li AU - Ma L AD - Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical College, Xincheng Road, Dongguan, 523808, P R China. marry806@163.com. FAU - Wu, Pengfei AU - Wu P AD - Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical College, Xincheng Road, Dongguan, 523808, P R China. 529947701@qq.com. AD - Department of Biochemistry, School of Basic Medicine, Guangdong Medical College, Dongguan, 523808, P R China. 529947701@qq.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150116 PL - England TA - BMC Biochem JT - BMC biochemistry JID - 101084098 RN - 0 (H2AX protein, human) RN - 0 (Histone Deacetylase Inhibitors) RN - 0 (Histones) RN - 107-92-6 (Butyric Acid) RN - 6PLQ3CP4P3 (Etoposide) SB - IM MH - Butyric Acid/*pharmacology MH - Cell Proliferation/drug effects MH - DNA Breaks, Double-Stranded/*drug effects MH - DNA Repair/*drug effects MH - Drug Synergism MH - Etoposide/*pharmacology MH - HEK293 Cells MH - Histone Deacetylase Inhibitors/*pharmacology MH - Histones/metabolism MH - Humans MH - MCF-7 Cells MH - S Phase/drug effects PMC - PMC4304611 EDAT- 2015/01/17 06:00 MHDA- 2016/01/30 06:00 PMCR- 2015/01/16 CRDT- 2015/01/17 06:00 PHST- 2014/10/17 00:00 [received] PHST- 2014/12/17 00:00 [accepted] PHST- 2015/01/17 06:00 [entrez] PHST- 2015/01/17 06:00 [pubmed] PHST- 2016/01/30 06:00 [medline] PHST- 2015/01/16 00:00 [pmc-release] AID - s12858-014-0030-5 [pii] AID - 30 [pii] AID - 10.1186/s12858-014-0030-5 [doi] PST - epublish SO - BMC Biochem. 2015 Jan 16;16:2. doi: 10.1186/s12858-014-0030-5.