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S-allyl-L-cysteine (SAC) is a sulfur compound present in fresh garlic. The reference literature describes its anticancer, antioxidant and neuroprotective effects. Breast cancer is infamously known as one of the most commonly diagnosed malignancies among women worldwide. Its morbidity and mortality make it reasonable to complete and expand knowledge on this cancer's characteristics. Hydrogen sulfide (H2S) and its naturally occurring donors are well-known investigation subjects for diverse therapeutic purposes. This study was conducted to investigate the SAC antiproliferative potential and effect on three enzymes involved in H2S metabolism: 3-mercaptopyruvate sulfurtransferase (MPST), cystathionine γ-lyase (CTH), and cystathionine β-synthase (CBS). We chose the in vitro cellular model of human breast adenocarcinomas: MCF-7 and MDA-MB-231. The expression of enzymes after 2, 4, 6, 8, and 24 h incubation with 2.24 mM, 3.37 mM, and 4.50 mM SAC concentrations was examined. The number of living cells was determined by the MTS assay. Changes in cellular plasma membrane integrity were measured by the LDH test. Expression changes at the protein level were analyzed using Western blot. A significant decrease in viable cells was registered for MCF-7 cells after all incubation times upon 4.50 mM SAC exposure, and after 6 and 24 h only in MDA-MB-231 upon 4.50 mM SAC. In both cell lines, the MPST gene expression significantly increased after the 24 h incubation with 4.50 mM SAC. S-allyl-L-cysteine had opposite effects on changes in CTH and CBS expression in both cell lines. In our research model, we confirmed the antiproliferative potential of SAC and concluded that our studies provided current information about the increase in MPST gene expression mediated by S-allyl-L-cysteine in the adenocarcinoma in vitro cellular model for the MCF-7 and MDA-MB-231 cell lines. Further investigation of this in vitro model can bring useful information regarding sulfur enzyme metabolism of breast adenocarcinoma and regulating its activity and expression (gene silencing) in anticancer therapy. [ABSTRACT FROM AUTHOR]

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Copyright of Advances in Hygiene & Experimental Medicine / Postepy Higieny i Medycyny Doswiadczalnej is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The rhodanese superfamily (EC 2.8.1.x) includes tandem-domain thiosulfate:cyanide sulfurtransferase (TST, EC 2.8.1.1) and the strictly related 3-mercaptopyruvate:cyanide sulfurtransferase (MPST, EC 2.8.1.2). TST is the key enzyme, in the active center of which the persulfide group is created. The highly reactive sulfane sulfur atom of this group can be transferred to a substrate, e.g., cyanide detoxification, or can be passed to another protein acceptor participating in different cellular processes, e.g., biosynthesis of cofactors or thionucleosides. MPST transfers the sulfur atom from mercaptopyruvate, a product of cysteine transamination, to acceptors, such as cyanide (forming thiocyanate) or sulfite (forming thiosulfate – a sulfane sulfur-containing compound). Several metabolic reactions are known to generate sulfane sulfur in vitro, but their relative importance in vivo is not yet known. Current knowledge about sulfur donors assumes that the primary source of sulfane sulfur in eukaryotic cells relies on l-cysteine desulfuration pathway. Gamma-cystathionase (CTH, EC 4.4.1.1), an enzyme on the pathway, participates in endogenous production of H2S from l-cysteine. A product of CTH reaction, thiocystine, has been suggested to serve as the sulfane sulfur donor substrate for rhodanese. The potential role of the sulfane sulfur pool as an H2S reservoir and factors influencing the activity of sulfane sulfur-generating enzymes are under debate. The current study demonstrates that the MPST-dependent mitochondrial H2S-producing pathway is affected by oxidative stress, what may attenuate the production of H2S, and leads to various pathophysiological conditions. The intriguing problem is to identify possible sulfane sulfur donor(s) and/or acceptor(s), and to determine the regulatory role of sulfur in cellular metabolism. [ABSTRACT FROM AUTHOR]