Characterization of the apoptotic response of human leukemia cells to organosulfur compounds.

Background: Novel therapeutic agents that selectively induce tumor cell death are urgently needed in the clinical management of cancers. Such agents would constitute effective adjuvant approaches to traditional chemotherapy regimens. Organosulfur compounds (OSCs), such as diallyl disulfide, have demonstrated anti-proliferative effects on cancer cells.

Reduction of disulfide bonds within anti-D results in enhanced Fcgamma receptor blockade.

Background: We have investigated whether chemicals known to disrupt disulfide bonds are capable of altering immunoglobulin anti-D structure resulting in an increased efficacy of the chemically modified anti-D to inhibit Fcgamma receptor (FcgammaR)-mediated phagocytosis. If successful, this would provide a rationale to explore this mechanism of enhancing FcgammaR blockade for future use in immunoglobulin therapies for immune cytopenias.

Study Design And Methods: Anti-D that was shown to block 50 percent of the FcgammaR-mediated phagocytosis of opsonized red blood cells (RBCs) using a monocyte monolayer assay (MMA) was combined with two different thiol-containing compounds, dithiothreitol (DTT) or p-toluenesulfonylmethyl mercaptan, with or without treatment with iodoacetamide, and allowed to react.

Cell cycle arrest and apoptosis responses of human breast epithelial cells to the synthetic organosulfur compound p-methoxyphenyl p-toluenesulfonate.

Background: There are several studies documenting that organosulfur compounds show promise as anticancer agents. Although some mechanisms of the antiproliferative activity of naturally occurring organosulfur compounds have been elucidated, few studies have reported the differential response of human breast cells to these compounds.

Materials And Methods: The effect of the synthetic sulfonate ester, p-methoxyphenyl p-toluenesulfonate on growth inhibitory activity depending upon the estrogen-receptor (ER), p53, bcl-2 and caspase-3 status of cells was investigated by comparing its effects on three distinct human breast cancer cell lines (MCF-7, MDA-MB-231 and MDA-MB-453) and on one normal human mammary epithelial cell line (MCF-10A).

Antiproliferative effects of a series of novel synthetic sulfonate esters on human breast cancer cell line MCF-7.

Background: It has been well documented that some organosulfur compounds (OACs) show promise as anticancer agents.

Materials And Methods: The growth inhibitory effects of six novel different synthetic sulfonate esters was evaluated on cancerous (MCF-7) and non-cancerous (MCF-10A) human breast epithelial cells.

Results: We found that the most active compounds against MCF-7 breast cancer cells had a common structure of p-methoxyphenyl p-toluenesulfonate with the methoxy substituent shifted from position 4 (22) to 2 (22o) or to 3 (22m).

Structure-function studies for in vitro chemical inhibition of Fc gamma receptor-mediated phagocytosis.

Background: Previous studies [Transfusion 2005;45:384] showed that certain chemical compounds containing sulfur-reactive groups can inhibit Fcgamma receptor (FcgammaR)-mediated phagocytosis in vitro. These studies, however, did not prove that only sulfur functionality-induced reactivity was efficacious. In an effort to develop a drug-based approach for the future treatment of immune-mediated cytopenias, these earlier findings have now been extended and this chemically induced interference with FcgammaR-mediated phagocytosis of anti-D-coated red cells (RBCs) was examined to assess the optimal structural requirements for the inhibitory effect.

Chemical compounds that target thiol-disulfide groups on mononuclear phagocytes inhibit immune mediated phagocytosis of red blood cells.

Background: Patients having immune cytopenias produce antibodies that target hematopoietic cells resulting in their phagocytosis and intracellular destruction. Early reports suggested that phagocytosis could be inhibited by interfering with membrane thiol (SH) groups on phagocytes. Thus, whether chemical compounds that interact with SH or disulfide (SS) groups on mononuclear phagocytes can inhibit phagocytosis of antibody-coated cells was examined.

Improving upon the in vitro biological activity of antithrombotic disulfides.

Several sulfur-containing compounds, isolated from garlic, have been implicated as highly active antithrombotic agents. We have prepared 10 new aromatic disulfides and an aromatic thiosulfonate in order to determine the in vitro response of human platelets to dosages of these compounds. The poor biological activity of PhSSCH3 was enhanced by the introduction of, inter alia, a nitro group onto the aromatic ring.