Cytotoxicity In Vitro, Apoptosis, Cellular Uptake, Cell Cycle Distribution, Mitochondrial Membrane Potential Detection, DNA Binding, and Photocleavage of Ruthenium(ii) Complexes
Gan-Jian Lin A , Zheng-Zheng Li A , Jun-Hua Yao B , Hong-Liang Huang C D , Yang-Yin Xie A and Yun-Jun Liu A DA School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
B Instrument Analysis and Research Center, Sun Yat-Sen Uiversity, Guangzhou, 510275, China.
C School of Life Science and Biopharmaceutical, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
D Corresponding authors. Email: hhongliang@163.com; lyjche@163.com
Australian Journal of Chemistry 66(5) 555-563 https://doi.org/10.1071/CH12564
Submitted: 7 November 2012 Accepted: 7 January 2013 Published: 5 February 2013
Abstract
Four new ruthenium(ii) complexes [Ru(bpy)2(NHPIP)](ClO4)2 (Ru-1), [Ru(phen)2(NHPIP)](ClO4)2 (Ru-2), [Ru(bpy)2(AHPIP)](ClO4)2 (Ru-3), and [Ru(phen)2(AHPIP)](ClO4)2 (Ru-4) (bpy = 2,2′-bipyridine; phen = 1,10-phenanthroline; NHPIP = 2-(3-nitro-4-hydroxylphenyl)imidazo[4,5-f][1,10]phenanthroline; AHPIP = 2-(3-amino-4-hydroxylphenyl)imidazo[4,5-f][1,10]phenanthroline) were synthesized and characterized by elemental analysis, electrospray mass spectrometry, and 1H NMR spectroscopy. The cytotoxicity in vitro of these complexes against BEL-7402, HeLa, MG-63, and MCF-7 cells was evaluated by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method. Ru-4 shows the highest cytotoxic activity towards the selected cell lines among the four complexes. The morphological apoptosis was assayed by an acridine orange/ethidium bromide staining method, and the percentages of necrotic and apoptotic cells were determined by flow cytometry. The cellular uptake and the cell cycle arrest in BEL-7402 cell was investigated. The results showed these complexes inhibit the proliferation of BEL-7402 cells at G0/G1 phase arrest. The detection of mitochondrial membrane potentials using the fluorescence probe JC-1 (5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolcarbocyanine iodide) exhibited that the mitochondrial membrane potentials decrease. Upon irradiation, these complexes can effectively cleave pBR322 DNA.
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