title: 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.
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 (52.4mgkg-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.
authors.affiliation: School of Bioscience and Veterinary Medicine, University of Camerino, Camerino, MC, 62032, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Montani
authors.affiliation: School of Bioscience and Veterinary Medicine, University of Camerino, Camerino, MC, 62032, Italy; School of Pharmacy, University of Camerino, Camerino, MC, 62032, Italy.
authors.forename: Gretta V Badillo
authors.initials: GVB
authors.lastname: Pazmay
authors.affiliation: Aging Research Centre, G. d⿿Annunzio University, Chieti, 66100, Italy.
authors.forename: Albana
authors.initials: A
authors.lastname: Hysi
authors.affiliation: School of Pharmacy, University of Camerino, Camerino, MC, 62032, Italy. Electronic address: giulio.lupidi@unicam.it.
authors.forename: Giulio
authors.initials: G
authors.lastname: Lupidi
authors.affiliation: School of Pharmacy, University of Camerino, Camerino, MC, 62032, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Pettinari
authors.affiliation: School of Bioscience and Veterinary Medicine, University of Camerino, Camerino, MC, 62032, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Gambini
authors.affiliation: School of Bioscience and Veterinary Medicine, University of Camerino, Camerino, MC, 62032, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Tilio
authors.affiliation: School of Science and Technology, University of Camerino, Camerino, MC, 62032, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Marchetti
authors.affiliation: School of Pharmacy, University of Camerino, Camerino, MC, 62032, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Pettinari
authors.affiliation: School of Science and Technology, University of Camerino, Camerino, MC, 62032, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferraro
authors.affiliation: Aging Research Centre, G. d⿿Annunzio University, Chieti, 66100, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Iezzi
authors.affiliation: School of Bioscience and Veterinary Medicine, University of Camerino, Camerino, MC, 62032, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Marchini
authors.affiliation: School of Bioscience and Veterinary Medicine, University of Camerino, Camerino, MC, 62032, Italy. Electronic address: augusto.amici@unicam.it.
authors.forename: Augusto
authors.initials: A
authors.lastname: Amici
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009942:Organometallic Compounds / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D012428:Ruthenium / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D012428:Ruthenium
keywords: Anticancer drugs; In vivo tests; Organometallic arene complexes; Ruthenium(II); Triple negative breast cancer; Tumor infiltrating regulatory T cells