Induction of histone acetylation in mouse erythroleukemia cells by some organosulfur compounds including allyl isothiocyanate

Abstract

In previous studies we observed that some allyl sulfides can cause increased acetylation of histones and differentiation in DS19 mouse erythroleukemia cells. In the present work we observed increased acetylation of histones with allyl isothiocyanate and butanethiol but not with butyl sulfide or butyl disulfide. Increased acetylation of histones was established by change in electrophoretic mobility, incorporation of [ 3 H]acetate or immunoblotting. Histone deacetylase in nuclei of DS19 cells was inhibited 74% by 0.5 mM allyl mercaptan and 43% by 0.5 mM butanethiol but was not significantly affected by 0.5 mM allyl isothiocyanate. There was some degree of reversibility in the effect of allyl isothiocyanate when the cells were incubated for 15 hr in fresh medium. The data suggested that allyl isothiocyanate may stimulate histone acetylation rather than inhibit histone deacetylation. Addition of allyl isothiocyanate, however, had very little or no additional effect on the induction of histone acetylation caused by trichostatin A. Histone acetyltransferase activity determined in cell homogenates was not increased by preincubation of cells with allyl isothiocyanate or inclusion of allyl isothiocyanate in the assay medium. It was concluded that treatment of mouse erythroleukemia cells with allyl isothiocyanate can cause increased acetylation of histones but the mechanism for this effect requires further elucidation.

Erk is involved in the differentiation induced by diallyl disulfide in the human gastric cancer cell line MGC803

“…All of the above indicated that DADS induced differentiation in MGC803 cells. Recently, other studies showed that DADS inhibits proliferation and induces differentiation through increased histone acetylation on rat liver and hepatoma and colon tumors [22,23]. The mechanism induced by DADS in MGC803 cells will be explored in our next study.…”

Plant Phytochemicals as Epigenetic Modulators: Role in Cancer Chemoprevention

“…This dual PEITC action was more effective than the pharmacological inhibitors of DNMT and HDACs (80). Allyl isothiocyanate treatment of DS19 mouse erythroleukemia cells increased the acetylation of histones with no effect on HDACs (81).…”

“…DADS treatment increased global acetylation of H3 and H4 histones and increased their binding on the promoter of p21 gene. These events correlated with HDAC inhibition, upregulation of p21 and cell cycle arrest (81). Treatment of human colon cancer Caco-2 cells and human breast cancer T47D cells with SAMC induced histone acetylation where HDAC activity was inhibited with allyl butyrate (93).…”

Naturally Occurring Organic Sulfur Compounds: An Example of a Multitasking Class of Phytochemicals in Anti-Cancer Research

“…Lea et al reported for the first time the increased acetylation of histones H3 and H4 in mouse erythroleukemia DS19 and human leukemia K562 after treatment with DADS and AM (Lea et al, 1999). Then, the same group has confirmed those effects in vivo as histone acetylation was induced in liver and Morris hepatoma 7777 in rats treated with DADS and AM (Lea & Randolph, 2001). Data suggested a direct link between histone hyperacetylation and the antiproliferative activity of some garlic components.…”