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Nickel(II) bis(isatin thiosemicarbazone) complexes induced apoptosis through mitochondrial signaling pathway and G0/G1 cell cycle arrest in IM-9 cells
Journal of Inorganic Biochemistry ( IF 3.9 ) Pub Date : 2018-02-24 , DOI: 10.1016/j.jinorgbio.2018.02.014
Chandrasekar Balachandran , Jebiti Haribabu , Kumaramangalam Jeyalakshmi , Nattamai S.P. Bhuvanesh , Ramasamy Karvembu , Nobuhiko Emi , Suresh Awale

Three novel complexes (1, 3 and 4) ligating N-substituted isatin thiosemicarbazone derivatives have been synthesized and their structural and biological characteristics have been compared with those of the known analogs (2, 57 and 8). In addition, the structure of the representative ligands (L1, L3 and L4) and complex (4) was confirmed by single crystal X-ray diffraction method. All the complexes (18) were assessed for their cytotoxic property against a panel of four human cancer cells such as HepG-2 (liver), MOLM-14 (acute monocytic leukemia), U937 (histiocytic lymphoma). and IM-9 (myeloma). Complex 4 exhibited prominent cytotoxic property against MOLM-14, U937 and IM-9 cell lines. Moreover, the results were compared with the well-known anticancer drugs like doxorubicin, cisplatin and daunorubicin. Besides, complex 4 enhanced the apoptotic cell death in IM-9 cell line and induced cell cycle arrest at G1 phase. Western blot analysis revealed the down-regulation of Bcl-2 (b-cell lymphoma-2), up-regulation of Bax (bcl-2 associated X protein), release of cytochrome c and activation of caspases-3 in IM-9 cells by complex 4. Importantly, complex 4 was not toxic to the normal Vero cell line (IC50 > 300 μM). In addition, complex 4 showed the concentration dependent cleavage of supercoiled (SC) DNA to its nicked circular (NC) form.



中文翻译:

镍(II)(isatin thiosemicarbazone)复合物通过线粒体信号通路和IM-9细胞中的G0 / G1细胞周期阻滞诱导凋亡

三个新的配合物(134)结扎ñ -取代的靛红缩氨基硫脲衍生物已被合成,并且它们的结构和生物学特性已与那些已知类似物的比较(25 - 78)。另外,通过单晶X射线衍射法确认了代表性的配体(L1,L3,L4)和配合物(4)的结构。所有复合体(18评估了它们对一组四种人类癌细胞如HepG-2(肝),MOLM-14(急性单核细胞白血病),U937(组织细胞性淋巴瘤)的细胞毒性。和IM-9(骨髓瘤)。复合物4对MOLM-14,U937和IM-9细胞系表现出突出的细胞毒性。此外,将结果与著名的抗癌药如阿霉素,顺铂和柔红霉素进行了比较。此外,复合物4增强IM-9细胞系中的凋亡细胞死亡并诱导细胞周期停滞在G1期。Western印迹分析显示IM-9细胞中Bcl-2(b细胞淋巴瘤2)的下调,Bax(bcl-2相关的X蛋白)的上调,细胞色素c的释放和caspases-3的激活复数4。重要的是,复合物4对正常的Vero细胞系无毒性(IC 50  > 300μM)。另外,复合物4显示出超螺旋(SC)DNA切割成有切口的环状(NC)形式的浓度依赖性切割。

更新日期:2018-02-24
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