Ruthenium (II) complex cis-[Ru(II)(ŋ(2)-O(2)CC(7)H(7)O(2))(dppm)(2)]PF(6)-hmxbato induces ROS-mediated apoptosis in lung tumor cells producing selective cytotoxicity.
Ruthenium (II) complex cis-[Ru(II)(ŋ(2)-O(2)CC(7)H(7)O(2))(dppm)(2)]PF(6)-hmxbato induces ROS-mediated apoptosis in lung tumor cells producing selective cytotoxicity.
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DOI：
10.1038/s41598-020-72420-w
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发表时间：
2020-09-21
影响因子：
4.6
通讯作者：
Yoneyama KAG
中科院分区：
文献类型：
--
作者：
Costa MS;Gonçalves YG;Borges BC;Silva MJB;Amstalden MK;Costa TR;Antunes LMG;Rodrigues RS;Rodrigues VM;de Faria Franca E;Zoia MAP;de Araújo TG;Goulart LR;Von Poelhsitz G;Yoneyama KAG
作为潜在的癌症治疗分子，Ru络合物已被广泛研究。考虑到我们以前的研究结果表明，3-羟基-4-甲氧基苯甲酸酯(Hmxbato)-顺-[RuII(ŋ2-O2CC7H7O2)(Dppm)2]PF6对利什曼原虫具有显著的细胞毒活性，并且锥虫与肿瘤细胞具有相似的代谢特征，本研究旨在分析Hmxbato对肺肿瘤细胞的抗癌作用及其部分死亡机制。Hmxbato对A549肺癌细胞具有选择性细胞毒作用。此外，在3.8µM的浓度下，该复合体能够显著增加肿瘤细胞中活性氧物种(ROS)的生成，导致氧化应激，最终可能导致：(1)细胞增殖减少；(2)细胞形态和肌动蛋白细胞骨架的组织模式发生变化；(3)细胞停滞在细胞周期的G2/M期；(4)细胞凋亡；(5)线粒体膜电位的变化和(6)初始DNA损伤。此外，我们还证明了细胞程序性死亡的诱导可以通过激活半胱氨酸天冬氨酸酶的内在凋亡途径发生。同样值得强调的是，与BEAS-2B正常支气管上皮细胞相比，hmxbato对A549肿瘤细胞显示了优越的作用，这使该复合体成为设计抗肺癌新药的有趣候选者。
Ruthenium complexes have been extensively explored as potential molecules for cancer treatment. Considering our previous findings on the remarkable cytotoxic activity exhibited by the ruthenium (II) complex 3-hydroxy-4-methoxybenzoate (hmxbato)-cis-[RuII(ŋ2-O2CC7H7O2)(dppm)2]PF6 against Leishmania promastigotes and also the similar metabolic characteristics between trypanosomatids and tumor cells, the present study aimed to analyze the anticancer potential of hmxbato against lung tumor cells, as well as the partial death mechanisms involved. Hmxbato demonstrated selective cytotoxicity against A549 lung tumor cells. In addition, this complex at a concentration of 3.8 µM was able to expressively increase the generation of reactive oxygen species (ROS) in tumor cells, causing an oxidative stress that may culminate in: (1) reduction in cellular proliferation; (2) changes in cell morphology and organization patterns of the actin cytoskeleton; (3) cell arrest in the G2/M phase of the cell cycle; (4) apoptosis; (5) changes in the mitochondrial membrane potential and (6) initial DNA damage. Furthermore, we demonstrated that the induction of programmed cell death can occur by the intrinsic apoptotic pathway through the activation of caspases. It is also worth highlighting that hmxbato exhibited predominant actions on A549 tumor cells in comparison to BEAS-2B normal bronchial epithelium cells, which makes this complex an interesting candidate for the design of new drugs against lung cancer.
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DOI：
10.1186/1478-811x-8-31
发表时间：
2010-12-22
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Chaitanya GV;Steven AJ;Babu PP
通讯作者：
Babu PP
水杨酸钌 (II) 复合物通过靶向硫氧还蛋白还原酶诱导 ROS 介导的细胞凋亡
影响因子：
3.9
作者：
Chen, Jin-can;Zhang, Yao;Chen, Lan-mei
通讯作者：
Chen, Lan-mei
影响因子：
5.1
作者：
De Grandis, Rone Aparecido;da Silva dos Santos, Patrick Wellington;Pavan, Fernando Rogerio
通讯作者：
Pavan, Fernando Rogerio
影响因子：
7.3
作者：
Caruso, Francesco;Rossi, Miriam;Pettinari, Claudio
通讯作者：
Pettinari, Claudio
影响因子：
3.9
作者：
Costa, Monica S.;Goncalves, Yasmim G.;Yoneyama, Kelly A. G.
通讯作者：
Yoneyama, Kelly A. G.