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BioMetals

, Volume 32, Issue 1, pp 21–32 | Cite as

Copper complex with sulfamethazine and 2,2′-bipyridine supported on mesoporous silica microspheres improves its antitumor action toward human osteosarcoma cells: cyto- and genotoxic effects

  • Juan Fernando Cadavid-Vargas
  • Pablo Maximiliano Arnal
  • Ruth Dary Mojica Sepúlveda
  • Andrea Rizzo
  • Delia Beatriz Soria
  • Ana Laura Di VirgilioEmail author
Article

Abstract

Ideal drugs to cure cancer leave normal cells unharmed while selectively turning tumor cells unviable. Several copper complexes have been able to selectively slow down tumor proliferation. We hypothesized that Cu(smz)2(bipy)·H2O (1)—a copper-complex that has two ligands capable of interacting with DNA—would outperform Cu(smz)2(OH2)·2H2O (2), and also that supporting 1 on mesoporous silica spheres would decrease even further tumor cell viability in vitro. After exposing osteosarcoma cells (MG-63) and normal phenotype cells of bone origin (MC3T3-E1) to either complex, we studied their toxic effect and mechanisms of action. We determined cell viability (MTT assay) and quantified formation of reactive oxygen species (oxidation of DHR-123 to rhodamine). Moreover, we assessed genotoxicity from (i) formation of micronucleus (MN assay) and (ii) damage of DNA (Comet assay). After the exposure of 1 supported on silica spheres, we tested cell viability. Our results confirm our hypotheses: inhibition of tumor cells follows: supported 1 > dissolved 1 > 2. Future work that enhances the load of the complex exclusively in mesopores may improve the ability of 1 to further inhibit tumor cell viability.

Keywords

Antitumor effect Copper(II) complexes Cytotoxicity Genotoxicity Mesoporous silica microspheres 

Notes

Acknowledgements

The work was supported by UNLP (11X/690), CONICET (PIP 0105), and ANPCyT (PICT 2014-2223, PICT 2014-2583 and PICT 2016-0508) from Argentina.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10534_2018_154_MOESM1_ESM.tif (282 kb)
Supplementary material 1 (TIFF 281 kb). Supplementary material Fig. 1. Electronic spectra of 1
10534_2018_154_MOESM2_ESM.png (36 kb)
Supplementary material 2 (PNG 35 kb). Supplementary material Fig. 2. FT- IR spectra of 1 (green), silica spheres (blue) and silica supported complex (red)
10534_2018_154_MOESM3_ESM.tif (93 kb)
Supplementary material 3 (TIFF 93 kb). Supplementary material Fig. 3. Thermal gravimetric analysis of the silica spheres (blue), 1 (green) and complex supported on silica spheres (red)
10534_2018_154_MOESM4_ESM.tif (466 kb)
Supplementary material 4 (TIFF 465 kb). Supplementary material Fig. 4. A. SEM image of silica spheres. B. complex supported on spheres. The arrow indicates a complex crystal. C. EDX spectra of silica supported 1
10534_2018_154_MOESM5_ESM.docx (14 kb)
Supplementary material 5 (DOCX 13 kb)

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Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.CEQUINOR (CONICET-UNLP), Facultad de Ciencias ExactasUniversidad Nacional de La PlataLa PlataArgentina
  2. 2.CETMIC (Centro de Tecnología de Recursos Minerales y Cerámica)M.B. GonnetArgentina
  3. 3.Facultad de Ciencias ExactasUniversidad Nacional de La PlataLa PlataArgentina

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