Ruthenium compounds have become promising alternatives to platinum drugs by displaying specific activities against different cancers and favorable toxicity and clearance properties. Here, we show that the ruthenium(II) complex [Ru(p-cymene)(bis(3,5-dimethylpyrazol-1-yl)methane)Cl]Cl (UNICAM-1) exhibits potent in vivo antitumor effects. When administered as four-dose course, by repeating a single dose (52.4 mg kg-1) every three days, UNICAM-1 significantly reduces the growth of A17 triple negative breast cancer cells transplanted into FVB syngeneic mice. Pharmacokinetic studies indicate that UNICAM-1 is rapidly eliminated from kidney, liver and bloodstream thanks to its high hydrosolubility, exerting excellent therapeutic activity with minimal side effects. Immunohistological analysis revealed that the efficacy of UNICAM-1, mainly relies on its capacity to reverse tumor-associated immune suppression by significantly reducing the number of tumor-infiltrating regulatory T cells. Therefore, UNICAM-1 appears very promising for the treatment of TNBC. © 2016 Elsevier Ltd. All rights reserved

The water soluble ruthenium(II) organometallic compound[Ru(p-cymene)(bis(3,5 dimethylpyrazol-1-yl)methane)Cl]Clsuppresses triple negative breast cancer growth by inhibiting tumorinfiltration of regulatory T cells

MONTANI, Maura;BADILLO PAZMAY, GRETTA VERONICA;LUPIDI, Giulio;PETTINARI, Riccardo;GAMBINI, VALENTINA;TILIO, MARTINA;MARCHETTI, Fabio;PETTINARI, Claudio;FERRARO, Stefano;MARCHINI, Cristina;AMICI, Augusto
2016-01-01

Abstract

Ruthenium compounds have become promising alternatives to platinum drugs by displaying specific activities against different cancers and favorable toxicity and clearance properties. Here, we show that the ruthenium(II) complex [Ru(p-cymene)(bis(3,5-dimethylpyrazol-1-yl)methane)Cl]Cl (UNICAM-1) exhibits potent in vivo antitumor effects. When administered as four-dose course, by repeating a single dose (52.4 mg kg-1) every three days, UNICAM-1 significantly reduces the growth of A17 triple negative breast cancer cells transplanted into FVB syngeneic mice. Pharmacokinetic studies indicate that UNICAM-1 is rapidly eliminated from kidney, liver and bloodstream thanks to its high hydrosolubility, exerting excellent therapeutic activity with minimal side effects. Immunohistological analysis revealed that the efficacy of UNICAM-1, mainly relies on its capacity to reverse tumor-associated immune suppression by significantly reducing the number of tumor-infiltrating regulatory T cells. Therefore, UNICAM-1 appears very promising for the treatment of TNBC. © 2016 Elsevier Ltd. All rights reserved
2016
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11581/391677
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