Synthesis, cytotoxic activities and cell cycle arrest profiles of half-sandwich N-sulfonamide based dithio-o-carborane metal complexes |
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Authors: | Huan Dou Wei Zhong Liu Yang Tingting Wang Hong Yan Yayi Hou |
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Institution: | Immunology and Reproductive Biology Lab and Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing 210093, China. |
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Abstract: | Two half-sandwich cobalt and rhodium complexes 2a and 2b with combination of carborane and N-Sulfonamide were synthesized and fully characterized by NMR spectroscopy, mass spectrometry, elemental analysis as well as X-ray crystallography. In an in vitro cytotoxicity assay toward the non-small cell lung cancer cell lines of A549 and NCI-H460, 2b showed the stronger activity than 2a, which was confirmed by the morphological test. Mechanistic studies for 2b showed that inhibition of NSCLC cell growth was mediated by G0/G1 cell cycle arrested without the significant apoptosis induction. Furthermore, 2b altered the mRNA levels of CCND1, CCNE1 and PCNA, which were known to control G0/G1 phase of the cell cycle. Our western blot analysis also showed that 2b-induced G0/G1 cell cycle arrest was mediated through the decreased expression of cyclin D1, cyclin E1 and PCNA. |
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