Chair of Medical Biochemistry, Jagiellonian University Medical College, 7 Kopernika St, 31-034, Kraków, Poland.
Department of Histology, Jagiellonian University Medical College, 7 Kopernika St, 31-034, Kraków, Poland.
Amino Acids. 2017 Nov;49(11):1855-1866. doi: 10.1007/s00726-017-2484-4. Epub 2017 Aug 29.
The study was conducted to elucidate the mechanism of antiproliferative and antioxidative action of diallyl trisulfide (DATS), a garlic-derived organosulfur compound. Changes in the L-cysteine desulfuration, and the levels of cystathionine and non-protein thiols in DATS-treated human glioblastoma (U87MG) and neuroblastoma (SH-SY5Y) cells were investigated. The inhibition of proliferation of the investigated cells by DATS was correlated with an increase in the inactivated form of Bcl-2. In U87MG cells, an increased level of sulfane sulfur and an increased activity of 3-mercaptopyruvate sulfurtransferase (MPST) and rhodanese, the enzymes involved in sulfane sulfur generation and transfer, suggest that DATS can function as a donor of sulfane sulfur atom, transferred by sulfurtransferases, to sulfhydryl groups of cysteine residues of Bcl-2 and in this way lower the level of active form of Bcl-2 by S-sulfuration. Diallyl trisulfide antioxidative effects result from an increased level of cystathionine, a precursor of cysteine, and an increased glutathione level. MPST and rhodanese, the level of which is increased in the presence of DATS, can serve as antioxidant proteins.
本研究旨在阐明大蒜衍生的有机硫化合物二烯丙基三硫（DATS）的抗增殖和抗氧化作用机制。研究了 DATS 处理的人神经胶质瘤（U87MG）和神经母细胞瘤（SH-SY5Y）细胞中 L-半胱氨酸脱硫、胱硫醚和非蛋白巯基水平的变化。DATS 对所研究细胞增殖的抑制作用与 Bcl-2 失活形式的增加相关。在 U87MG 细胞中，磺基丙氨酸水平升高，3-巯基丙酮酸硫转移酶（MPST）和 rhodanese 的活性增加，这两种酶参与磺基硫的生成和转移，表明 DATS 可以作为磺基硫原子的供体，通过硫转移酶转移到 Bcl-2 半胱氨酸残基的巯基上，从而通过 S-磺化降低 Bcl-2 的活性形式水平。二烯丙基三硫的抗氧化作用源于胱硫醚水平的升高，胱硫醚是半胱氨酸的前体，谷胱甘肽水平也随之升高。存在 DATS 时，MPST 和 rhodanese 的水平升高，可作为抗氧化蛋白。
