Biological evaluation of new nickel(II) metallates: Synthesis, DNA/protein binding and mitochondrial mediated apoptosis in human lung cancer cells (A549) via ROS hypergeneration and depletion of cellular antioxidant pool
Biological evaluation of new nickel(II) metallates: Synthesis, DNA/protein binding and mitochondrial mediated apoptosis in human lung cancer cells (A549) via ROS hypergeneration and depletion of cellular antioxidant pool
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DOI：
10.1016/j.ejmech.2014.05.075
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发表时间：
2014-07-23
影响因子：
6.7
通讯作者：
Natarajan, K.
中科院分区：
文献类型：
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作者：
Kalaivani, P.;Saranya, S.;Natarajan, K.
合成了一系列新型的镍（11）缩氨基硫脲配合物（1-4），并通过各种光谱、分析技术和X射线晶体学进行了表征。此外，已经探索了它们与CT-DNA/BSA相互作用的功效。从结合研究中可以推断，发现络合物4比其他络合物更有活性。配合物与CT-DNA以嵌入方式结合。此外，观察到静态猝灭与BSA的相互作用。用体外细胞毒性试验检测了配合物对人肺腺癌细胞株A549的细胞毒性。结果表明，在一定的实验条件下，新配合物具有明显的细胞毒性。此外，LDH和NO释放的结果支持复合物的细胞毒性性质。复合物的细胞毒性可能是通过ROS过度生成和脂质过氧化，随后细胞抗氧化剂库（GSH，SOD，CAT，GPx和GST）的消耗导致细胞膜电位降低，caspase-3激活和DNA片段化。因此，本研究的数据显示，配合物可以通过线粒体介导的方式诱导A549细胞凋亡，并抑制肺癌细胞的迁移和转移。(C)2014年Elsevier Masson SAS。All rights reserved.
A series of novel nickel(11) thiosemicarbazone complexes(1-4) have been prepared and characterized by various spectral, analytical techniques and X-ray crystallography. Further, their efficacy to interact with CT-DNA/BSA has been explored. From the binding studies, it is inferred that complex 4 found to be more active than other complexes. The complexes bound with CT-DNA by intercalation mode. Moreover, static quenching was observed for their interaction with BSA. The new complexes were tested for their in vitro cytotoxicity against human lung adenocarcinoma (A549) cell line. The results showed that the new complexes exhibited significant degree of cytotoxicity at given experimental condition. Further, the results of LDH and NO release supported the cytotoxic nature of the complexes. The observed cytotoxicity of the complexes may be routed through ROS-hypergeneration and lipid-peroxidation with subsequent depletion of cellular antioxidant pool (GSH, SOD, CAT, GPx and GST) resulted in the reduction of mitochondrial-membrane potential, caspase-3 activation and DNA fragmentation. Thus, the data from the present study disclose that the complexes could induce apoptosis in A549 cells through mitochondrial mediated fashion and inhibited the migration of lung cancer cells and by metastasis. (C) 2014 Elsevier Masson SAS. All rights reserved.