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Cytotoxicity, apoptosis, cell cycle arrest, reactive oxygen species, mitochondrial membrane potential, and Western blotting analysis of ruthenium(II) complexes

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Abstract

Three new ruthenium(II) complexes—[Ru(bpy)2(adppz)](ClO4)2, [Ru(dmb)2(adppz)](ClO4)2, and [Ru(dmp)2(adppz)](ClO4)2 (bpy is 2,2′-bipyridine, adppz is 7-aminodipyrido[3,2-a:2′,3′-c]phenazine, dmb is 4,4′-dimethyl-2,2′-bipyridine, and dmp is 2,9-dimethyl-1,10-phenanthroline)—were synthesized. [Ru(dmp)2(adppz)](ClO4)2 exhibits higher cytotoxicity than cisplatin toward A549, MG-63, and SKBR-3 cells. The apoptosis and cellular uptake were studied by fluorescence microscopy. [Ru(dmp)2(adppz)](ClO4)2 enhances the level of reactive oxygen species (ROS) and decreases the mitochondrial membrane potential. These complexes induce cell cycle arrest in S phase in BEL-7402 cells, and inhibit the antiproliferation of SKBR-3 cells at G0/G1 phase. Western blotting analysis shows that [Ru(dmp)2(adppz)](ClO4)2 induces apoptosis in BEL-7402 cells through activation of caspase 3, caspase 7, and procaspase 7 and ROS-mediated mitochondrial dysfunction pathways.

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Acknowledgments

This work was supported by the National Nature Science Foundation of China (no. 31070858) and Guangdong Pharmaceutical University.

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Authors and Affiliations

  1. School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China

    Gan-Jian Lin, Guang-Bin Jiang, Yang-Yin Xie, Zhen-Hua Liang & Yun-Jun Liu

  2. School of Life Science and Biopharmaceutical, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China

    Hong-Liang Huang

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  1. Gan-Jian Lin
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  2. Guang-Bin Jiang
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  3. Yang-Yin Xie
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Correspondence to Hong-Liang Huang or Yun-Jun Liu.

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Lin, GJ., Jiang, GB., Xie, YY. et al. Cytotoxicity, apoptosis, cell cycle arrest, reactive oxygen species, mitochondrial membrane potential, and Western blotting analysis of ruthenium(II) complexes. J Biol Inorg Chem 18, 873–882 (2013). https://doi.org/10.1007/s00775-013-1032-2

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  • DOI: https://doi.org/10.1007/s00775-013-1032-2

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