The water soluble ruthenium(II) organometallic compound [Ru(p-cymene)(bis(3, 5 dimethylpyrazol-1-yl)methane)Cl]Cl suppresses triple negative breast cancer growth by inhibiting tumor infiltration of regulatory T cells. (May 2016)

• Record Type: Journal Article
• Authors: Montani, Maura; Pazmay, Gretta V. Badillo; Hysi, Albana; Lupidi, Giulio; Pettinari, Riccardo; Gambini, Valentina; Tilio, Martina; Marchetti, Fabio; Pettinari, Claudio; Ferraro, Stefano; Iezzi, Manuela; Marchini, Cristina; Amici, Augusto
• Is Part Of: Pharmacological research. Volume 107(2016:May)
• Page Start: 282
• Page End: 290
• Publication Date: 2016-05
• Subjects: Ruthenium(II) -- Organometallic arene complexes -- Anticancer drugs -- Triple negative breast cancer -- In vivo tests -- Tumor infiltrating regulatory T cells; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2016.03.032
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: 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.