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Pharmacol Res ; 107: 282-290, 2016 05.
Article in English | MEDLINE | ID: mdl-27038531

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.


Subject(s)
Antineoplastic Agents/therapeutic use , Organometallic Compounds/therapeutic use , Ruthenium/therapeutic use , Triple Negative Breast Neoplasms/drug therapy , Animals , Antineoplastic Agents/blood , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Female , Humans , Kidney/metabolism , Liver/drug effects , Liver/metabolism , Liver/pathology , Mice , Organometallic Compounds/blood , Organometallic Compounds/pharmacokinetics , Organometallic Compounds/pharmacology , Ruthenium/blood , Ruthenium/pharmacokinetics , Ruthenium/pharmacology , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/immunology , Triple Negative Breast Neoplasms/immunology , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology , Tumor Burden/drug effects
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