Abstract:
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.
摘要:
S-烯丙基-L-半胱氨酸(SAC)是新鲜大蒜中存在的硫化合物。参考文献描述了它的抗癌,抗氧化和神经保护作用。众所周知,乳腺癌是全球女性中最常见的恶性肿瘤之一。它的发病率和死亡率使我们合理地完成和扩大对这种癌症特征的认识。硫化氢(H2S)及其天然存在的供体是用于多种治疗目的的众所周知的研究对象。进行这项研究是为了研究SAC的抗增殖潜力和对参与H2S代谢的三种酶的影响:3-巯基丙酮酸硫转移酶(MPST),胱硫醚γ-裂解酶(CTH),和胱硫醚β-合成酶(CBS)。我们选择了人乳腺腺癌的体外细胞模型:MCF-7和MDA-MB-231。与2.24mM孵育2、4、6、8和24h后的酶的表达,3.37mM,并检查4.50mMSAC浓度。通过MTS测定确定活细胞的数量。通过LDH测试测量细胞质膜完整性的变化。使用蛋白质印迹分析蛋白质水平的表达变化。在4.50mMSAC暴露后的所有孵育时间后,MCF-7细胞的活细胞显着减少,6和24小时后仅在MDA-MB-231中使用4.50mMSAC。在两种细胞系中,与4.50mMSAC孵育24小时后,MPST基因表达显着增加。S-烯丙基-L-半胱氨酸对两种细胞系中CTH和CBS表达的变化具有相反的作用。在我们的研究模型中,我们证实了SAC的抗增殖潜力,并得出结论,我们的研究提供了关于MCF-7和MDA-MB-231细胞系的腺癌体外细胞模型中S-烯丙基-L-半胱氨酸介导的MPST基因表达增加的最新信息.对该体外模型的进一步研究可以带来有关乳腺癌硫酶代谢以及在抗癌治疗中调节其活性和表达(基因沉默)的有用信息。