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Anti-tumor activity and mechanism of apoptosis of A549 induced by ruthenium complex

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Abstract

Two new ruthenium (II) polypyridyl complexes [Ru(MeIm)4(pip)]2+ (1) and [Ru(MeIm)4(4-npip)]2+ (2) were synthesized under the guidance of computational studies (DFT). Their binding property to human telomeric G-quadruplex studied by UV–Vis absorption spectroscopy, the fluorescent resonance energy transfer (FRET) melting assay and circular dichroism (CD) spectroscopy for validating the theoretical prediction. Both of them were evaluated for their potential anti-proliferative activity against four human tumor cell lines. Complex 2 shows growth inhibition against all the cell lines tested, especially the human lung tumor cell (A549). The RTCA analysis not only validated the inhibition activity but also showed the ability of reducing A549 cells’ migration. DNA-flow cytometric analysis, mitochondrial membrane potential (ΔΨm) and the scavenger measurements of reactive oxygen species (ROS) analysis carried out to investigate the mechanism of cell growth inhibition and apoptosis-inducing effect of complex 2. The results demonstrated that complex 2 induces tumor cells apoptosis by acting on both mitochondrial homeostasis destruction and death receptor signaling pathways. And those suggested that complex 2 could be a candidate for further evaluation as a chemotherapeutic agent against human tumor.

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Acknowledgments

We would like to thank our co-workers of the biotechnology center of Anhui Agriculture University for their technical supports. This work was supported by the National Natural Science Foundation of China (21401002), the Natural Science Foundation of Anhui Province, China (1508085QB37), the Youth Science Fund Key Project of Anhui Agricultural University (2013ZR011). This research leading to these results has also received funding from the Science Foundation of Young Teachers of Anhui Agricultural University (ZHSJ2013057), and the New Specialty of Biopharmaceutical Construction of Anhui Agricultural University (SJJD201313).

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    Authors and Affiliations

    1. A School of life sciences, Anhui Agricultural University, Hefei, 230036, China

      Dongdong Sun, Zhipeng Mou, Nuan Li, Weiwei Zhang, Yazhe Wang, Endong Yang & Weiyun Wang

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    1. Dongdong Sun
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    2. Zhipeng Mou
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    4. Weiwei Zhang
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    Correspondence to Weiyun Wang.

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    D. Sun and Z. Mou contribute equally to this work.

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    Sun, D., Mou, Z., Li, N. et al. Anti-tumor activity and mechanism of apoptosis of A549 induced by ruthenium complex. J Biol Inorg Chem 21, 945–956 (2016). https://doi.org/10.1007/s00775-016-1391-6

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    • DOI: https://doi.org/10.1007/s00775-016-1391-6

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