Ruthenium complex exerts antineoplastic effects that are mediated by oxidative stress without inducing toxicity in Walker-256 tumor-bearing rats

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...

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Vydáno v:	Free radical biology & medicine Ročník 110; s. 228 - 239
Hlavní autoři:	Alves de Souza, Carlos Eduardo, Alves de Souza, Helen de Morais, Stipp, Maria Carolina, Corso, Claudia Rita, Galindo, Claudia Martins, Cardoso, Carolina Riverin, Dittrich, Rosangela Locatelli, de Souza Ramos, Edneia Amancio, Klassen, Giseli, Carlos, Rose Maria, Correia Cadena, Sílvia Maria Suter, Acco, Alexandra
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Elsevier Inc 01.09.2017
Témata:	Animals Antineoplastic Agents - chemical synthesis Antineoplastic Agents - pharmacology bcl-2-Associated X Protein - genetics bcl-2-Associated X Protein - metabolism Carcinoma 256, Walker - drug therapy Carcinoma 256, Walker - genetics Carcinoma 256, Walker - metabolism Carcinoma 256, Walker - pathology Caspase 3 - genetics Caspase 3 - metabolism Cell Respiration - drug effects Cell Survival - drug effects Coordination Complexes - chemical synthesis Coordination Complexes - pharmacology Drug Evaluation, Preclinical Gene Expression Regulation, Neoplastic Injections, Subcutaneous Male Necrosis - chemically induced Necrosis - genetics Necrosis - metabolism Oxidative stress Oxidative Stress - drug effects Proto-Oncogene Proteins c-bcl-2 - genetics Proto-Oncogene Proteins c-bcl-2 - metabolism Rats Rats, Wistar Reactive Oxygen Species - agonists Reactive Oxygen Species - metabolism RuphenImH Ruthenium Ruthenium - chemistry Ruthenium - pharmacology Tumor Tumor Burden - drug effects Tumor Cells, Cultured Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism Walker-256 Rats Oxidative stress Tumor RuphenImH Ruthenium Walker-256
ISSN:	0891-5849, 1873-4596, 1873-4596
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Shrnutí:	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 10mgkg−1 RuC orally or intraperitoneally (i.p.) every 3 days for 13 days. A positive control group (2mgkg−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 (10mgkg−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. [Display omitted] •The compound RuphenImH (RuC) presented antitumor effect against the Walker-256 tumor in rats.•RuC induced oxidative stress and reduced the respiration of tumor cells.•RuC presented antitumor effect by i.p. but not by p.o. administration.•RuC has antitumor effect without causing systemic toxicity.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0891-5849 1873-4596 1873-4596
DOI:	10.1016/j.freeradbiomed.2017.06.011