The effect of 1:2 Ag(I) thiocyanate complexes in MCF-7 breast cancer cells

Abstract

There is much interest currently in the design of metal compounds as drugs and various metal compounds are already in clinical use. These include gold(I) compounds such as auranofin and the anti-cancer platinum(II) complex, cisplatin. Bis-chelated gold(I) phosphine complexes have also shown great potential as anticancer agents, however, their efficacy has been limited by their high toxicity. In this study, silver(I) thiocyanate compounds linked to four specific ligands, were synthesized and characterized. These silver-phosphine adducts included [AgSCN{P(4-MeC6H4)3}2]2 (1); [AgSCN{P(4-ClC6H4)3}2]2 (2); [AgSCN{P(4-MeOC6H4)3}2]2 (3); [AgSCN(PPh3)2]2 (4). The compounds were found to be toxic to MCF-7 breast cancer cells while the ligands on their own were not toxic. Our findings further indicate that the silver(I) phosphine compounds induce apoptotic cell death in these breast cancer cells. In addition, the compounds were not toxic to nonmalignant fibroblast cells at the IC50 concentrations. This is an indication that the compounds show selectivity towards the cancer cells.

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Abbreviations

13C:

Carbon 13 NMR

CDCl3 :

Deuterated chloroform

CDDP:

Cis-diamine-dichloro platinum (cisplatin)

CHNS:

Carbon, hydrogen, nitrogen, sulphur elemental analysis

DMSO:

Dimethyl sulfoxide

FITC:

Fluorescein isothiocyanate

1H:

Proton NMR

IC50 :

Half maximal inhibitory concentration

IR:

Infra red spectrometry

J:

J-coupling constant

LMS:

Leiomyosarcoma cell

Mp:

Melting point

NMR:

Nuclear magnetic resonance spectrometry

31P:

Phosphorous 31 NMR

PI:

Propidium iodide

PPh3 :

Triphenylphosphine

PS:

Phosphatidylserine

SEM:

Standard error of the mean

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Acknowledgments

This work is based on the research supported in the part by the National Research Foundation of South Africa (Grant specific unique reference number (UID 85386)). We would like also to thank the University of Johannesburg for funding.

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Correspondence to Marianne J. Cronjé.

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Ferreira, E., Munyaneza, A., Omondi, B. et al. The effect of 1:2 Ag(I) thiocyanate complexes in MCF-7 breast cancer cells. Biometals 28, 765–781 (2015). https://doi.org/10.1007/s10534-015-9865-5

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Keywords

  • Silver-phosphine complexes
  • Apoptosis
  • Flow-cytometry
  • MCF-7 breast cancer cells
  • Anti-cancer
  • Drug discovery