Effect of S-Allyl –L-Cysteine on MCF-7 Cell Line 3-Mercaptopyruvate Sulfurtransferase/Sulfane Sulfur System, Viability and Apoptosis

Abstract

The S-Allyl-L-cysteine (SAC) component of aged garlic extract (AGE) is proven to have anticancer, antihepatotoxic, neuroprotective and neurotrophic properties. γ-Cystathionase (CTH), cystathionine β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (MPST) are involved in H2S/sulfane sulfur endogenous formation from L-cysteine. The aim of the study was to determine the effect of SAC on MCF-7 cells survival and apoptosis, which is a widely known approach to reduce the number of cancer cells. An additional goal of this paper was to investigate the effect of SAC on the activity and expression of enzymes involved in H2S production. The experiments were carried out in the human breast adenocarcinoma cell line MCF-7. Changes in the cell viability were determined by MTT assay. Cell survival was determined by flow cytometry (FC). Changes in enzymes expression were analyzed using Western blot. After 24 h and 48 h incubation with 2245 µM SAC, induction of late apoptosis was observed. A decrease in cell viability was observed with increasing SAC concentration and incubation time. SAC had no significant cytotoxic effect on the MCF-7 cells upon all analyzed concentrations. CTH, MPST and CBS expression were confirmed in non-treated MCF-7 cells. Significant decrease in MPST activity at 2245 µM SAC after 24 h and 48 h incubation vs. 1000 µM SAC was associated with decrease in sulfane sulfur levels. The presented results show promising SAC effects regarding the deterioration of the MCF-7 cells’ condition in reducing their viability through the downregulation of MPST expression and sulfate sulfur level reduction.

MPST deficiency promotes intestinal epithelial cell apoptosis and aggravates inflammatory bowel disease via AKT

“…In addition, increased MPST activity alleviated intestinal apoptosis in a TNF-α-induced cell model. Consistent with our results, a previous study also showed that apoptosis was efficiently induced through the addition of S-Allyl-L-Cysteine, while there was a significant decrease in MPST activity in the MCF-7-cell line [ 15 ]. Thus, MPST might play an important role in regulating intestinal apoptosis activity and might be a potential therapeutic target for IBD.…”

“…MPST activity is also known to be involved in tRNA thiolation, protein urmylation and cyanide detoxification [ 14 ]. Tissue-specific changes in MPST expression correlate with aging and the development of metabolic disease [ 14 , 15 ]. To date, whether MPST is involved in the regulation of inflammation and in the pathogenesis of UC remains unknown.…”

From Natural Sources to Synthetic Derivatives: The Allyl Motif as a Powerful Tool for Fragment-Based Design in Cancer Treatment

“…These studies also found that 6 reduced colony formation in a dosedependent manner. 81 This garlic-derived compound was also tested in an experimental model of breast cancer in combination with doxorubicin (21), a chemotherapeutic agent. The synergistic treatment effect markedly decreased tumor volume and weight, increased animals' survival rate, and attenuated doxorubicin-induced tumor inflammation.…”

“…20 The significant decrease in mercaptopyruvate sulfurtransferase (MPST) and sulfane sulfur levels was one explanation of the promising effects of SAC on the deterioration of the MCF-7 cells' condition. 21 In a search for new anticancer molecules, molecule containing nonivamide (11), a less pungent analog of capsaicin and SAC (8), was developed (Figure 4). Molecular docking studies and dynamics simulation analysis suggested the potential for a stable interaction and favorable binding of the hybrid molecule 12 with therapeutic target proteins that included the human estrogen receptor α (ER-α), tumor protein negative regulator mouse double minute 2 (MDM2), B-cell lymphoma 2 (Bcl-2), and cyclin-dependent kinase 2 (CDK2) to treat cancer.…”

“… 20 The significant decrease in mercaptopyruvate sulfurtransferase (MPST) and sulfane sulfur levels was one explanation of the promising effects of SAC on the deterioration of the MCF-7 cells’ condition. 21 …”