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Antiproliferative activity and apoptosis induction, of organo-antimony(III)–copper(I) conjugates, against human breast cancer cells

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Abstract

Three known organo-antimony(III)–copper(I), mixed-metal small bioactive molecules (SBAMs) of formula [Cu(tpSb)3Cl] (1), [Cu2(tpSb)4Br2] (2) and [Cu2(tpSb)4I2] (3) (tpSb = triphenylstibine) were used for the clarification of their antiproliferative activity against human breast cancer cells: MCF-7 (hormone-dependent cells) and MDA-MB-231 (hormone-independent cells). The in vitro toxicity of 1–3 was studied against normal human foetal lung fibroblast cells (MRC-5). The genotoxicity of 1–3 was determined by the presence of micronucleus. The type of the cell death caused by 1–3 was determined using cell cycle arrest. The molecular mechanism of action of 1–3 was defined by their binding affinity towards CT-DNA (calf thymus DNA) using UV spectroscopy and viscosity measurements. Docking studies depict the interactions between 1–3 and DNA. Computations were also employed in order to rationalize the activity of these compounds. This is based on the contribution of metal aromaticity in the case of compounds 2 and 3 where the short Cu···Cu distance (2.7724(6) (2) and 2.7251(11) (3) Ǻ, respectively) suggests d10–d10 interaction between metal centres.

Graphic abstract

The known small bioactive molecules of formula [Cu(tpSb)3Cl] (1), [Cu2(tpSb)4Br2] (2) and [Cu2(tpSb)4I2] (3) (tpSb = triphenylstibine) were used for the clarification of their antiproliferative activity against human breast cancer cells: MCF-7 (hormone-dependent (HD) cells) and MDA-MB-231 (hormone-independent (HI) cells).

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Acknowledgements

This work was carried out for the fulfilment of the requirements for the B.Sc. thesis of Mr. K.K. according to the curriculum of the Department of Biological Applications and Technology of the University of Ioannina under the supervision of SKH. CNB and SKH would like to thank the Unit of Bioactivity Testing of Xenobiotics of the University of Ioannina for providing access to the facilities. CNB and SKH would like to thank the Atherothrombosis Research Centre of the University of Ioannina for providing access to the flow cytometer and to the fluorescence microscopy. This research has been co-financed by the European Union and Greek national funds through the Operational Program Competitiveness, Entrepreneurship and Innovation, under the call RESEARCH – CREATE – INNOVATE (Project Code: T1EDK-02990).

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Authors and Affiliations

  1. Section of Inorganic and Analytical Chemistry, Department of Chemistry, University of Ioannina, 45110, Ioannina, Greece

    C. N. Banti, V. Tsiatouras, K. Karanicolas & S. K. Hadjikakou

  2. Department of Chemistry, University of Cyprus, 1678, Nicosia, Cyprus

    N. Panagiotou & A. J. Tasiopoulos

  3. Medical Physics Laboratory, Medical School, University of Ioannina, Ioannina, Greece

    N. Kourkoumelis

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  1. C. N. Banti
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Banti, C.N., Tsiatouras, V., Karanicolas, K. et al. Antiproliferative activity and apoptosis induction, of organo-antimony(III)–copper(I) conjugates, against human breast cancer cells. Mol Divers 24, 1095–1106 (2020). https://doi.org/10.1007/s11030-019-10014-z

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