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Characterization of antiproliferative potential and biological targets of a copper compound containing 4′-phenyl terpyridine

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Abstract

Several copper complexes have been assessed as anti-tumor agents against cancer cells. In this work, a copper compound [Cu(H2O){OS(CH3)2}L](NO3)2 incorporating the ligand 4′-phenyl-terpyridine antiproliferative activity against human colorectal, hepatocellular carcinomas and breast adenocarcinoma cell lines was determined, demonstrating high cytotoxicity. The compound is able to induce apoptosis and a slight delay in cancer cell cycle progression, probably by its interaction with DNA and induction of double-strand pDNA cleavage, which is enhanced by oxidative mechanisms. Moreover, proteomic studies indicate that the compound induces alterations in proteins involved in cytoskeleton maintenance, cell cycle progression and apoptosis, corroborating its antiproliferative potential.

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Acknowledgments

We thank FCT/MEC for financial support (PTDC/BBB-NAN/1812/2012; PEst-OE/QUI/UI0100/2013). We also thank A. Silva, J. Palma, L. Coito and J. Silva for technical support; and G. Cabral (CEDOC, FCM/UNL) for technical support with flow cytometry assays.

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Authors and Affiliations

  1. Departamento de Ciências da Vida, UCIBIO, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, Campus de Caparica, 2829-516, Caparica, Portugal

    Ana Soraia Mendo, Sara Figueiredo, Catarina Roma-Rodrigues, Paula A. Videira, Pedro V. Baptista & Alexandra R. Fernandes

  2. Departamento de Ciências da Vida, Nanomedicine@FCT, CIGMH, UCIBIO, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Campus da Caparica, 2829-516, Caparica, Portugal

    Sara Figueiredo, Miguel Larguinho & Pedro V. Baptista

  3. CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056, Lisbon, Portugal

    Paula A. Videira

  4. Centro de Química Estrutural, Complexo 1, Instituto Superior Técnico, Universidade de Lisboa, Avenida Rovisco Pais, 1049-001, Lisbon, Portugal

    Zhen Ma, Armando J. L. Pombeiro & Alexandra R. Fernandes

  5. UCIBIO, REQUIMTE, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Campus de Caparica, 2829-516, Caparica, Portugal

    Mário Diniz & Miguel Larguinho

  6. Departamento de Ciências e Engenharia do Ambiente, MARE-Marine and Environmental Sciences Centre, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Campus de Caparica, 2829-516, Caparica, Portugal

    Pedro M. Costa

  7. LAQV, REQUIMTE, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Campus de Caparica, 2829-516, Caparica, Portugal

    João C. Lima

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  1. Ana Soraia Mendo
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  2. Sara Figueiredo
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Correspondence to Alexandra R. Fernandes.

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Mendo, A.S., Figueiredo, S., Roma-Rodrigues, C. et al. Characterization of antiproliferative potential and biological targets of a copper compound containing 4′-phenyl terpyridine. J Biol Inorg Chem 20, 935–948 (2015). https://doi.org/10.1007/s00775-015-1277-z

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