Induction of histone acetylation and inhibition of growth of mouse erythroleukemia cells by S-allylmercaptocysteine.
Growth-inhibitory effects on DS19 mouse erythroleukemia cells were seen in the micromolar concentration range with allicin and S-allylmercaptocysteine and in the millimolar range with allyl butyrate, allyl phenyl sulfone, and S-allyl cysteine. Increased acetylation of histones was induced by incubation of cells with the allyl compounds at concentrations similar to those that resulted in the inhibition of cell proliferation. The induction of histone acetylation by S-allylmercaptocysteine was also observed in Caco-2 human colon cancer cells and T47D human breast cancer cells. In contrast to the effect on histone acetylation, there was a decrease in the incorporation of phosphate into histones when DS19 cells were incubated with 25 microM S-allylmercaptocysteine. Histone deacetylase activity was inhibited by allyl butyrate, but there was little or no effect with the allyl sulfur compounds examined in this study. A similar degree of downregulation of histone deacetylase and histone acetyltransferase was observed when DS19 cells were incubated with S-allylmercaptocysteine or allyl isothiocyanate. The induction of histone acetylation by S-allylmercaptocysteine was not blocked by a proteasome inhibitor. The mechanism by which S-allylmercaptocysteine induces histone acetylation remains to be characterized. It may be related in part to metabolism to allyl mercaptan, which is a more effective inhibitor of histone deacetylase.
Lea
Michael A
MA
Department of Biochemistry and Molecular Biology, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA. lea@umdnj.edu
Rasheed
Mariam
M
Randolph
Verrell M
VM
Khan
Faika
F
Shareef
Asif
A
desBordes
Charles
C
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism; D000498:Allyl Compounds / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004220:Disulfides; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism*; D007976:Leupeptins / Q000378:metabolism; D051379:Mice; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013441:Sulfinic Acids / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000378:metabolism
D000498:Allyl Compounds; D000970:Antineoplastic Agents; D004220:Disulfides; D006657:Histones; D007976:Leupeptins; C086300:S-allylmercaptocysteine; D029701:Saccharomyces cerevisiae Proteins; D013441:Sulfinic Acids; C006452:allicin; C065299:S-allylcysteine; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases; D003545:Cysteine; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde