Antitumour and Toxicity Evaluation of a Ru(II)-Cyclopentadienyl Complex in a Prostate Cancer Model by Imaging Tools
| Autor: | Fernanda Marques, Lurdes Gano, Ana Isabel Tomaz, Francisco Tortosa, Tânia S. Morais, A. P. Alves de Matos, Andreia Valente, Teresa Pinheiro, Marta Martins, Tiago F. Jorge, Maria L. S. Gonçalves, Maria Helena Garcia |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Cancer Research Antineoplastic Agents Cyclopentanes Pharmacology Ruthenium Nephrotoxicity 03 medical and health sciences 0302 clinical medicine Coordination Complexes In vivo Cell Line Tumor medicine Humans 030304 developmental biology Liver injury Cisplatin 0303 health sciences Dose-Response Relationship Drug Chemistry Prostatic Neoplasms Effective renal plasma flow medicine.disease Liver Mechanism of action 030220 oncology & carcinogenesis Toxicity Cancer cell Molecular Medicine medicine.symptom medicine.drug |
| Zdroj: | Anti-Cancer Agents in Medicinal Chemistry. 19:1262-1275 |
| ISSN: | 1871-5206 |
| Popis: | Background:Ruthenium complexes have been extensively investigated for their prospective value as alternatives to cisplatin. Recently, we reported the in vitro anticancer properties of a family of organometallic ruthenium( II)-cyclopentadienyl complexes and have explored their mechanism of action.Objective:The purpose of this study was to evaluate the in vivo antitumour efficacy and toxicity of one of these Ru(II) compounds, [RuCp(mTPPMSNa)(2,2′-bipy)][CF3SO2] (TM85) which displayed an interesting spectrum of activity against several cancer cells.Methods:Studies to assess the antitumour activity and toxicity were performed in a metastatic prostate (PC3) mice model using ICP-MS, nuclear microscopy, elemental analysis and Transmission Electron Microscopy (TEM).Results:TM85 showed low systemic toxicity but no significant tumour reduction, when administered at tolerated dose (20mg/kg) over 10 days. Ru was mainly retained in the liver and less in kidneys, with low accumulation in tumour. Increased bilirubin levels, anomalous Ca and Fe concentrations in liver and mitochondria alterations were indicative of liver injury. The hepatotoxicity observed was less severe than that of cisplatin and no nephrotoxicity was found.Conclusion:Under the experimental conditions of this study, TM85 is less toxic than cisplatin, induces similar tumour reduction and avoids the formation of metastatic foci. No renal toxicity was observed by the analysis of creatinine levels and the effective renal plasma flow by 99mTc-MAG3 clearance. Hence, it can be considered a valuable compound for further studies in the field of Ru-based anticancer drugs. |
| Databáze: | OpenAIRE |
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