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Ruthenium(II) polypyridyl complexes: synthesis, cytotoxicity in vitro, reactive oxygen species, mitochondrial membrane potential and cell cycle arrest studies

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Abstract

Two Ru(II) polypyridyl complexes [Ru(dmb)2(idpq)](ClO4)2 (1) (idpq = indeno[1,2-b]dipyrido[3,2-f:2′,3′-h]-quinoxaline-6-one, dmb = 4,4′-dimethyl-2,2′-bipyridine) and [Ru(bpy)2(idpq)](ClO4)2 (2) (bpy = 2,2′-bipyridine) have been synthesized and characterized. Their in vitro cytotoxicities, apoptosis, cellular uptake, production of reactive oxygen species (ROS), mitochondrial membrane potential assays and effects on cell cycle distribution were studied. The IC50 values range from 13.1 ± 1.1 to 30.9 ± 3.1 μM. Complex 1 is toxic to HeLa cells with an IC50 value of 13.1 ± 1.1 μM, while complex 2 shows relatively high cytotoxicity against HepG-2 cells. However, both complexes exhibit lower cytotoxicity than cisplatin toward selected cell lines under identical conditions. Both complexes can induce apoptosis and cell cycle arrest at the S and G0/G1 phases in HeLa cells, respectively. In addition, both Ru(II) complexes, which can be effectively taken up by HeLa cells, induced generation of intracellular ROS in a concentration-dependent manner and produced a decrease in mitochondrial membrane potential. The results show that these complexes induce apoptosis in HeLa cells through a ROS-mediated mitochondrial dysfunction pathway.

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Acknowledgments

This work was supported by the High-Level Personnel Project of Guangdong Province in 2013, the Fund of Guangdong Provincial Department of Science and Technology (2013B02180083) and the Joint Nature Science Fund of the Department of the Science and Technology and the First Affiliated Hospital of Guangdong Pharmaceutical University (No. GYFYLH201315).

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Authors and Affiliations

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

    Bing-Jie Han, Guang-Bin Jiang, Ji Wang, Wei Li, Qiu-Shuang Dai, Yang-Yin Xie, Gan-Jian Lin & Yun-Jun Liu

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

    Hong-Liang Huang

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  1. Bing-Jie Han
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  2. Guang-Bin Jiang
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Correspondence to Hong-Liang Huang or Yun-Jun Liu.

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Han, BJ., Jiang, GB., Wang, J. et al. Ruthenium(II) polypyridyl complexes: synthesis, cytotoxicity in vitro, reactive oxygen species, mitochondrial membrane potential and cell cycle arrest studies. Transition Met Chem 40, 153–160 (2015). https://doi.org/10.1007/s11243-014-9901-2

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  • DOI: https://doi.org/10.1007/s11243-014-9901-2

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