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The induction of apoptosis in SGC-7901 cells through the ROS-mediated mitochondrial dysfunction pathway by a Ir(III) complex

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Abstract

A new ligand BTCP and its iridium(III) complex [Ir(ppy)2(BTCP)]PF6 (Ir-1) were synthesized and characterized by elemental analysis, ESI–MS, IR, 1H NMR and 13C NMR. The cytotoxic activity in vitro of the ligand and its complex against SGC-7901, HeLa, HOS, PC-12, BEL-7402, MG-63, SiHa, A549, HepG2 and normal cell LO2 were evaluated by MTT method [MTT = (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)]. The apoptosis was assayed with AO/EB and Hoechst 33258 staining methods. The reactive oxygen species (ROS), mitochondrial membrane potential, autophagy and cell invasion were studied under fluorescent microscope. The expression of caspases and Bcl-2 family proteins were investigated by western blot. The IC50 values of complex toward SGC-7901, BEL-7402 and MG-63 cells are 3.9 ± 0.5, 5.4 ± 1.2 and 4.2 ± 0.6 µM. The complex can increase the levels of ROS, and induce a decrease in the mitochondrial membrane potential. Ir-1 inhibits the cell growth at G0/G1 phase in SGC-7901 cells, and the complex can induce both autophagy and apoptosis and inhibit the cell invasion. And the complex induces apoptosis through a ROS-mediated mitochondrial dysfunction pathway.

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Acknowledgements

This work was supported by the Natural Science foundation of Guangdong Province (No. 2016A030313728), the High-Level Personnel Project of Guangdong Province in 2013 and the Joint Nature Science Fund of the Department of Science and Technology and the First Affiliated Hospital of Guangdong Pharmaceutical University (No GYFYLH201315) and Project of Innovation for Enhancing Guangdong Pharmaceutical University, Provincial Experimental Teaching Demonstration Center of Chemistry and Chemical Engineering.

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Authors and Affiliations

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

    Cheng Zhang, Shang-Hai Lai, Chuan-Chuan Zeng, Bing Tang, Dan Wan & Yun-Jun Liu

  2. Guangdong Cosmetics Engineering and Technology Research Center, Guangzhou, 510006, People’s Republic of China

    Yun-Jun Liu

  3. School of Basic Science, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China

    De-Gang Xing

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  1. Cheng Zhang
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Correspondence to De-Gang Xing or Yun-Jun Liu.

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Zhang, C., Lai, SH., Zeng, CC. et al. The induction of apoptosis in SGC-7901 cells through the ROS-mediated mitochondrial dysfunction pathway by a Ir(III) complex. J Biol Inorg Chem 21, 1047–1060 (2016). https://doi.org/10.1007/s00775-016-1401-8

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