Glutathione-garlic sulfur conjugates: slow hydrogen sulfide releasing agents for therapeutic applications.
Glutathione-garlic sulfur conjugates: slow hydrogen sulfide releasing agents for therapeutic applications.
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DOI：
10.3390/molecules20011731
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发表时间：
2015-01-20
期刊：
影响因子：
--
通讯作者：
Melino S
中科院分区：
文献类型：
--
作者：
Bhuiyan AI;Papajani VT;Paci M;Melino S
大蒜中的天然有机硫化合物。显示出抗氧化和化学增敏特性，包括通过诱导细胞凋亡体外抑制肿瘤细胞增殖。大蒜水溶性和油溶性烯丙基硫化合物显示出独特的性质和抑制肿瘤细胞增殖的能力。在本研究中，我们优化了一种新的方案，用于在低温下从大蒜中提取水溶性化合物，并在提取过程中产生谷胱甘肽-OSC缀合物。自发的Cys/GSH混合二硫键缀合物通过OSC的体内代谢产生，并且代表能够影响细胞代谢的活性分子。水溶性提取物，（GSGaWS）或没有（GaWS）谷胱甘肽共轭物，在这里生产和测试其释放硫化氢（H2S）的能力，也在还原剂和硫代硫酸盐：氰化物硫转移酶（TST）酶的存在下。因此，通过体外分子实验研究了TST对大蒜OSCs及其缀合物释放H2S的催化作用。观察到这些提取物对人T细胞淋巴瘤细胞系HuT 78的抗增殖特性，并与组蛋白过度乙酰化和GAPDH表达下调有关。总而言之，这里提出的结果为生产GSGaWS作为新的缓释硫化氢提取物用于潜在的治疗应用铺平了道路。
Natural organosulfur compounds (OSCs) from Allium sativum L. display antioxidant and chemo-sensitization properties, including the in vitro inhibition of tumor cell proliferation through the induction of apoptosis. Garlic water- and oil-soluble allyl sulfur compounds show distinct properties and the capability to inhibit the proliferation of tumor cells. In the present study, we optimized a new protocol for the extraction of water-soluble compounds from garlic at low temperatures and the production of glutathionyl-OSC conjugates during the extraction. Spontaneously, Cys/GSH-mixed-disulfide conjugates are produced by in vivo metabolism of OSCs and represent active molecules able to affect cellular metabolism. Water-soluble extracts, with (GSGaWS) or without (GaWS) glutathione conjugates, were here produced and tested for their ability to release hydrogen sulfide (H2S), also in the presence of reductants and of thiosulfate:cyanide sulfurtransferase (TST) enzyme. Thus, the TST catalysis of the H2S-release from garlic OSCs and their conjugates has been investigated by molecular in vitro experiments. The antiproliferative properties of these extracts on the human T-cell lymphoma cell line, HuT 78, were observed and related to histone hyperacetylation and downregulation of GAPDH expression. Altogether, the results presented here pave the way for the production of a GSGaWS as new, slowly-releasing hydrogen sulfide extract for potential therapeutic applications.
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