Department of Biochemistry and Molecular and Cellular Biology, University of Zaragoza, C/Pedro Cerbuna 12, Zaragoza, Spain.
J Inorg Biochem. 2011 Oct;105(10):1306-13. doi: 10.1016/j.jinorgbio.2011.06.004. Epub 2011 Jun 24.
Gold compounds are being investigated as potential antitumor drugs. Some gold(III) derivatives have been shown to induce cell death in solid tumors but their mechanism of action differs from that of cisplatin, since most of these compounds do not bind to DNA. We have explored cellular events triggered by three different iminophosphorane-organogold(III) compounds in leukemia cells (a neutral compound with two chloride ligands [Au{κ(2)-C,N-C(6)H(4)(PPh(2)=N(C(6)H(5))-2}Cl(2)] 1, and two cationic compounds with either a dithiocarbamate ligand [Au{κ(2)-C,N-C(6)H(4)(PPh(2)=N(C(6)H(5))-2}(S(2)CN-Me(2))]PF(6)2, or a water-soluble phosphine and a chloride ligand [Au{κ(2)-C,N-C(6)H(4)(PPh(2)=N(C(6)H(5))-2}(P{Cp(m-C(6)H(4)-SO(3)Na)(2)}(3)) Cl]PF(6)3). All three compounds showed higher toxicity against leukemia cells when compared to normal T-lymphocytes. Compounds 1 and 2 induced both necrosis and apoptosis, while 3 was mainly apoptotic. Necrotic cell death induced by 1 and 2 was Bax/Bak- and caspase-independent, while apoptosis induced by 3 was Bax/Bak-dependent. Reactive oxygen species (ROS) production at the mitochondrial level was a critical step in the antitumor effect of these compounds.
金化合物正被作为潜在的抗肿瘤药物进行研究。一些金（III）衍生物已被证明能诱导实体瘤细胞死亡，但它们的作用机制与顺铂不同，因为这些化合物大多不与 DNA 结合。我们研究了三种不同的亚膦酰胺-有机金（III）化合物在白血病细胞中引发的细胞事件（一种具有两个氯配体的中性化合物[Au{κ(2)-C，N-C(6)H(4)(PPh(2)=N(C(6)H(5))-2}Cl(2)]1，以及两种带有二硫代氨基甲酸盐配体的阳离子化合物[Au{κ(2)-C，N-C(6)H(4)(PPh(2)=N(C(6)H(5))-2}(S(2)CN-Me(2))]PF(6)2，或一种水溶性膦和一个氯配体[Au{κ(2)-C，N-C(6)H(4)(PPh(2)=N(C(6)H(5))-2}(P{Cp(m-C(6)H(4)-SO(3)Na)(2)}(3))Cl]PF(6)3）。与正常 T 淋巴细胞相比，这三种化合物对白血病细胞的毒性都更高。化合物 1 和 2 均诱导坏死和凋亡，而 3 主要诱导凋亡。1 和 2 诱导的坏死性细胞死亡不依赖 Bax/Bak 和半胱天冬酶，而 3 诱导的凋亡依赖 Bax/Bak。线粒体水平的活性氧（ROS）产生是这些化合物抗肿瘤作用的关键步骤。
