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

  • C. N. BantiEmail author
  • V. Tsiatouras
  • K. Karanicolas
  • N. Panagiotou
  • A. J. Tasiopoulos
  • N. KourkoumelisEmail author
  • S. K. HadjikakouEmail author
Original Article
  • 33 Downloads

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 d10d10 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).

Keywords

Metal biology Metallotherapeutics Copper(I)–antimony(III) complexes Cytotoxic activity Breast cancer 

Notes

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).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11030_2019_10014_MOESM1_ESM.doc (6 mb)
Supplementary material 1 (DOC 6100 kb)

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Section of Inorganic and Analytical Chemistry, Department of ChemistryUniversity of IoanninaIoanninaGreece
  2. 2.Department of ChemistryUniversity of CyprusNicosiaCyprus
  3. 3.Medical Physics Laboratory, Medical SchoolUniversity of IoanninaIoanninaGreece

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