title: Histone deacetylase inhibitor sodium butyrate suppresses DNA double strand break repair induced by etoposide more effectively in MCF-7 cells than in HEK293 cells.
abstract: 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 γ-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.
authors.affiliation: Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical College, Xincheng Road, Dongguan, 523808, P R China. lipinggdmc@126.com.|Department of Biochemistry, School of Basic Medicine, Guangdong Medical College, Dongguan, 523808, P R China. lipinggdmc@126.com.
authors.forename: Liping
authors.initials: L
authors.lastname: Li
authors.affiliation: Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical College, Xincheng Road, Dongguan, 523808, P R China. sunyouxang@aliyun.com.|Department of Biochemistry, School of Basic Medicine, Guangdong Medical College, Dongguan, 523808, P R China. sunyouxang@aliyun.com.
authors.forename: Youxiang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical College, Xincheng Road, Dongguan, 523808, P R China. qliuj@yahoo.com.
authors.forename: Jiangqin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical College, Xincheng Road, Dongguan, 523808, P R China. 843348164@qq.com.|Department of Biochemistry, School of Basic Medicine, Guangdong Medical College, Dongguan, 523808, P R China. 843348164@qq.com.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Wu
authors.affiliation: Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical College, Xincheng Road, Dongguan, 523808, P R China. 573394815@qq.com.|Department of Biochemistry, School of Basic Medicine, Guangdong Medical College, Dongguan, 523808, P R China. 573394815@qq.com.
authors.forename: Lijun
authors.initials: L
authors.lastname: Chen
authors.affiliation: Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical College, Xincheng Road, Dongguan, 523808, P R China. marry806@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical College, Xincheng Road, Dongguan, 523808, P R China. 529947701@qq.com.|Department of Biochemistry, School of Basic Medicine, Guangdong Medical College, Dongguan, 523808, P R China. 529947701@qq.com.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Wu
mesh_terms: D020148:Butyric Acid / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D004357:Drug Synergism; D005047:Etoposide / Q000494:pharmacology*; D057809:HEK293 Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D016196:S Phase / Q000187:drug effects
chemical_list: C468783:H2AX protein, human; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D020148:Butyric Acid; D005047:Etoposide