Ruthenium complex exerts antineoplastic effects that are mediated by oxidative stress without inducing toxicity in Walker-256 tumor-bearing rats
| Autor: | Rose M. Carlos, Edneia A.S. Ramos, Carlos Eduardo Alves de Souza, Alexandra Acco, Helen de Morais Alves de Souza, Maria Carolina Stipp, Claudia Martins Galindo, Carolina R. Cardoso, Giseli Klassen, Silvia Maria Suter Correia Cadena, Rosangela Locatelli Dittrich, Claudia Rita Corso |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Programmed cell death Necrosis Cell Survival Injections Subcutaneous Cell Respiration Drug Evaluation Preclinical Antineoplastic Agents Pharmacology medicine.disease_cause Biochemistry Ruthenium 03 medical and health sciences In vivo Coordination Complexes Physiology (medical) medicine Tumor Cells Cultured Animals Carcinoma 256 Walker Rats Wistar bcl-2-Associated X Protein Cisplatin Chemistry Caspase 3 Rats Tumor Burden Gene Expression Regulation Neoplastic Oxidative Stress 030104 developmental biology Proto-Oncogene Proteins c-bcl-2 Apoptosis Tumor progression Toxicity Immunology medicine.symptom Tumor Suppressor Protein p53 Reactive Oxygen Species Oxidative stress medicine.drug |
| Zdroj: | Free radical biologymedicine. 110 |
| ISSN: | 1873-4596 |
| Popis: | The present study evaluated the in vivo antitumor effects and toxicity of a new Ru(II) compound, cis-(Ru[phen]2[ImH]2)2+ (also called RuphenImH [RuC]), against Walker-256 carcinosarcoma in rats. After subcutaneous inoculation of Walker-256 cells in the right pelvic limb, male Wistar rats received 5 or 10 mg kg−1 RuC orally or intraperitoneally (i.p.) every 3 days for 13 days. A positive control group (2 mg kg−1 cisplatin) and negative control group (vehicle) were also used. Tumor progression was checked daily. After treatment, tumor weight, plasma biochemistry, hematology, oxidative stress, histology, and tumor cell respiration were evaluated. RuC was effective against tumors when administered i.p. but not orally. The highest i.p. dose of RuC (10 mg kg−1) significantly reduced tumor volume and weight, induced oxidative stress in tumor tissue, reduced the respiration of tumor cells, and induced necrosis but did not induce apoptosis in the tumor. No clinical signs of toxicity or death were observed in tumor-bearing or healthy rats that were treated with RuC. These results suggest that RuC has antitumor activity through the modulation of oxidative stress and impairment of oxidative phosphorylation, thus promoting Walker-256 cell death without causing systemic toxicity. These effects make RuC a promising anticancer drug for clinical evaluation. |
| Databáze: | OpenAIRE |
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