Antitumor activity of [Pt(O,O'-acac)(γ-acac)(DMS)] in mouse xenograft model of breast cancer

A. Muscella, C. Vetrugno, D. Migoni, F. Biagioni, F. P. Fanizzi, F. Fornai, S. A. De Pascali, S. Marsigliante

Research output: Contribution to journalArticle

Abstract

The higher and selective cytotoxicity of [Pt(O,O'-acac)(γ-acac)(DMS)] toward cancer cell in both immortalized cell lines and in breast cancer cells in primary cultures, stimulated a pre-clinical study so as to evaluate its therapeutic potential in vivo. The efficacy of [Pt(O,O'-acac)(γ-acac)(DMS) ] was assessed using a xenograft model of breast cancer developed by injection of MCF-7 cells in the flank of BALB/c nude mice. Treatment of solid tumor-bearing mice with [Pt(O,O'-acac)(γ-acac)(DMS)] induced up to 50% reduction of tumor mass compared with an average 10% inhibition recorded in cisplatin-treated animals. Thus, chemotherapy with [Pt(O,O'-acac)(γ-acac) (DMS)] was much more effective than cisplatin. We also demonstrated enhanced in vivo pharmacokinetics, biodistribution and tolerability of [Pt(O,O'-acac) (γ-acac)(DMS)] when compared with cisplatin administered in Wistar rats. Pharmacokinetics studies with [Pt(O,O'-acac)(γ-acac)(DMS)] revealed prolonged Pt persistence in systemic blood circulation and decreased nefrotoxicity and hepatotoxicity, major target sites of cisplatin toxicity. Overall, [Pt(O,O'-acac)(γ-acac)(DMS)] turned out to be extremely promising in terms of greater in vivo anticancer activity, reduced nephrotoxicity and acute toxicity compared with cisplatin.

Original languageEnglish
Article numbere1014
JournalCell Death and Disease
Volume5
Issue number1
DOIs
Publication statusPublished - 2014

Keywords

  • Anticancer agents
  • Breast cancer
  • Cisplatin
  • Pharmacokinetic
  • Pt(II)-analogs

ASJC Scopus subject areas

  • Cell Biology
  • Immunology
  • Cancer Research
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Antitumor activity of [Pt(O,O'-acac)(γ-acac)(DMS)] in mouse xenograft model of breast cancer'. Together they form a unique fingerprint.

  • Cite this

    Muscella, A., Vetrugno, C., Migoni, D., Biagioni, F., Fanizzi, F. P., Fornai, F., De Pascali, S. A., & Marsigliante, S. (2014). Antitumor activity of [Pt(O,O'-acac)(γ-acac)(DMS)] in mouse xenograft model of breast cancer. Cell Death and Disease, 5(1), [e1014]. https://doi.org/10.1038/cddis.2013.554