s-allylmercaptocysteine and Breast-Neoplasms

Recently, an important topic of breast cancer had been published in 2013. In this report, estrogen receptor (ESR1) had defined the relation of hormone-cause breast cancer. The screening of traditional Chinese medicine (TCM) database has found the molecular compounds by simulating molecular docking and molecular dynamics to regulate ESR1. S-Allylmercaptocysteine and 5-hydroxy-L-tryptophan are selected according to the highest docking score than that of other TCM compounds and Raloxifene (control). The simulation from molecular dynamics is helpful in analyzing and detecting the protein-ligand interactions. After a comparing the control and the Apo form, then based on the docking poses, hydrophobic interactions, hydrogen bond and structure variations, this research postulates that S-allylmercaptocysteine may be more appropriate than other compounds for protein-ligand interaction.

Topics: 5-Hydroxytryptophan; Binding Sites; Breast Neoplasms; Computational Biology; Computer Simulation; Crystallography, X-Ray; Cysteine; Databases, Factual; Drug Design; Estrogen Receptor alpha; Female; Humans; Ligands; Medicine, Chinese Traditional; Molecular Docking Simulation; Protein Binding; Protein Conformation; Proteins

S-allyl mercaptocysteine (SAMC), a water-soluble component derived from garlic, has been found to exert multi-antitumor activities. This study was to investigate the responsible molecular mechanisms of SAMC in human breast cancer cell lines.. Sulforhodamine B assay was used to determine cell viability, flow cytometry was applied for the analysis of cell cycle and cell apoptosis, the change of protein was detected by Western blot.. It was found that SAMC exhibited an effective cell growth inhibition of human breast cancer cell lines MCF-7 (ER positive) and MDA-MB-231 (ER negative) in a dose- and time-dependent manner by inducing cell cycle arrested in G0/G1 phase, the block of cell cycle was associated with the up-regulation of p53 and p21. Furthermore, the SAMC-mediated cell cycle arrest was accompanied with promotion of apoptosis, as indicated by the changes in the nuclear morphology and expressions of apoptosis-related proteins. SAMC clearly triggered the mitochondrial apoptotic pathway as indicated by activation of Bax, decreased expression of Bcl-2 and Bcl-XL, and subsequent activation of caspase-9 and caspase-3.. These results highlight the value of a continued investigation into the use of SAMC as a potential antitumor candidate for breast cancer.

Topics: Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Cycle; Cell Line, Tumor; Cell Survival; Cysteine; Female; Humans; MCF-7 Cells

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.

Topics: Acetylation; Acetyltransferases; Allyl Compounds; Animals; Antineoplastic Agents; Breast Neoplasms; Colonic Neoplasms; Cysteine; Disulfides; Electrophoresis, Polyacrylamide Gel; Female; Histone Acetyltransferases; Histone Deacetylases; Histones; Humans; Leukemia, Erythroblastic, Acute; Leupeptins; Mice; Saccharomyces cerevisiae Proteins; Sulfinic Acids; Tumor Cells, Cultured

Organosulfur compounds are the biologically active components of allium vegetables. Many health benefits have been ascribed to them, including inhibition of carcinogenesis. Inasmuch as several of these thioallyl compounds are quite unstable and others are rapidly inactivated in the body, we have investigated one of the stable components present in aged garlic extract, S-allylmercaptocysteine (SAMC), in an effort to determine whether it can inhibit proliferation of cancer cells. Proliferation and viability of two erythroleukemia cell lines, HEL and OCIM-1, two hormone-responsive breast and prostate cancer cell lines, MCF-7 and CRL-1740, respectively, and normal human umbilical vein endothelial cells in response to different concentrations of SAMC were studied for up to two weeks. There were variations in sensitivity to this organosulfur compound in the different cell lines examined, but the two hormone-responsive cancer cell lines of breast and prostate clearly were far more susceptible to the growth-inhibitory influence of the thioallyl compound. The antiproliferative effect of SAMC was limited to actively growing cells. Human umbilical vein endothelial cells that had reached confluence escaped the reduction in viability so noticeable in the cancer cell lines tested. Our studies thus give evidence of a direct effect of SAMC on established cancer cells.

Topics: Antineoplastic Agents; Breast Neoplasms; Cell Division; Cell Survival; Cysteine; Humans; Leukemia, Erythroblastic, Acute; Male; Prostatic Neoplasms; Tumor Cells, Cultured