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Water-soluble platinum phthalocyanines as potential antitumor agents

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Abstract

Breast cancer represents the second cause of death in the European female population. The lack of specific therapies together with its high invasive potential are the major problems associated to such a tumor. In the last three decades platinum-based drugs have been considered essential constituents of many therapeutic strategies, even though with side effects and frequent generation of drug resistance. These drugs have been the guide for the research, in last years, of novel platinum and ruthenium based compounds, able to overcome these limitations. In this work, ruthenium and platinum based phthalocyanines were synthesized through conventional techniques and their antiproliferative and/or cytotoxic actions were tested. Normal mammary gland (MCF10A) and several models of mammarian carcinoma at different degrees of invasiveness (BT474, MCF-7 and MDA-MB-231) were used. Cells were treated with different concentrations (5–100 μM) of the above reported compounds, to evaluate toxic concentration and to underline possible dose–response effects. The study included growth curves made by trypan blue exclusion test and scratch assay to study cellular motility and its possible negative modulation by phthalocyanine. Moreover, we investigated cell cycle and apoptosis through flow cytometry and AMNIS Image Stream cytometer. Among all the tested drugs, tetrasulfonated phthalocyanine of platinum resulted to be the molecule with the best cytostatic action on neoplastic cell lines at the concentration of 30 μM. Interestingly, platinum tetrasulfophtalocyanine, at low doses, had no antiproliferative effects on normal cells. Therefore, such platinum complex, appears to be a promising drug for mammarian carcinoma treatment.

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Abbreviations

ICP MS:

Inductively-coupled-plasma mass-spectrometry

DMEM:

Dulbecco’s modified Eagle medium

PcS:

Tetrasulfophthalocyanina

PtPcS:

Platinum (II) tetrasulfonated phthalocyanine

PtPcC:

Platinum (II) tetracarboxylated phthalocyanine

RuPcS:

Ruthenium (II) tetrasulfonated phthalocyanine

RuPcC:

Ruthenium (II) tetracarboxylated phthalocyanine

RuPcAlkC:

β-Tetrapentylcarboxylated ruthenium (II) phthalocyanine

RPMI:

Roswell Park Memorial Institute

DMEM/F12:

Dulbecco’s modified Eagle medium: Nutrient mixture F-12

PI:

Propidium iodide

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Acknowledgments

The authors are grateful for financial support to the “Ministero dell’Università e della Ricerca” (MIUR) for PRIN Project: 2008F5A3AF_004, (Metal-phthalocyanines as potential antitumor drugs) and FIRB Project 2010. The present research was also supported by “Carichieti” foundation, Chieti, Italy.

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Authors and Affiliations

  1. Department of Medicine and Aging Science, School of Medicine and Health Sciences, University “G. d’Annunzio” of Chieti-Pescara, Via dei Vestini, 31, 66013, Chieti Scalo, Italy

    Giuseppina Bologna, Paola Lanuti, Laura Pierdomenico, Carlo D’Emilio, Marco Marchisio, Eugenio Santavenere & Sebastiano Miscia

  2. Department of Engineering and Geology (INGEO), University “G. d’Annunzio” of Chieti-Pescara, Viale Pindaro, 42, 65127, Pescara, Italy

    Primiano D’Ambrosio, Nicola d’Alessandro & Mario Bressan

  3. Department of Philosophical, Educational and Economic Science, University “G. d’Annunzio” of Chieti-Pescara, Via dei Vestini, 31, 66013, Chieti Scalo, Italy

    Lucia Tonucci

  4. Center for Ageing Sciences (Ce.S.I.), University “G. d’Annunzio” Foundation, Via dei Vestini, 31, 66013, Chieti Scalo, Italy

    Giuseppina Bologna, Paola Lanuti, Laura Pierdomenico, Carlo D’Emilio, Marco Marchisio, Eugenio Santavenere & Sebastiano Miscia

  5. Environmental Sciences Center, Mario Negri Sud Foundation, Via Nazionale 8/A, 66030, Santa Maria Imbaro, CH, Italy

    Nicola Celli

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  1. Giuseppina Bologna
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  2. Paola Lanuti
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  3. Primiano D’Ambrosio
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  4. Lucia Tonucci
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  6. Carlo D’Emilio
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  9. Nicola d’Alessandro
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  10. Eugenio Santavenere
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  11. Mario Bressan
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  12. Sebastiano Miscia
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Corresponding authors

Correspondence to Marco Marchisio or Nicola d’Alessandro.

Additional information

Giuseppina Bologna, Paola Lanuti, Primiano D’Ambrosio, Lucia Tonucci have contributed equally in this work.

Mario Bressan, Sebastiano Miscia, have equal senior authorship.

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Bologna, G., Lanuti, P., D’Ambrosio, P. et al. Water-soluble platinum phthalocyanines as potential antitumor agents. Biometals 27, 575–589 (2014). https://doi.org/10.1007/s10534-014-9730-y

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