☆ 4.6 Article

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 (2018)

期刊

JOURNAL OF INORGANIC BIOCHEMISTRY

卷 182, 期 -, 页码 208-221

出版社

ELSEVIER SCIENCE INC

DOI: 10.1016/j.jinorgbio.2018.02.014

关键词

Isatin thiosemicarbazones; Nickel(II) complexes; Cytotoxicity; Apoptosis; DNA cleavage

类别

Biochemistry & Molecular Biology Chemistry, Inorganic & Nuclear

资金

University Grants Commission [F1-17.1/2012-13/RGNF-2012-13-ST-AND-18716]

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摘要

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, 5-7 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 (1-8) 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 Bc1-2 (b-cell lymphoma-2), up-regulation of Bax (bc1-2 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 mu M). In addition, complex 4 showed the concentration dependent cleavage of supercoiled (SC) DNA to its nicked circular (NC) form.

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