RESUMO
The high toxicity and low selectivity of carmustine restrict its application in anticancer therapy. Therefore, proline analogs of nitrosourea have been synthesized to obtain compounds whose action on neoplastic cells is characterized by higher selectivity. The present studies have aimed at examining the influence of carmustine and a new proline analog of nitrosourea on the redox system of fibroblasts and breast cancer cells (MCF-7). Carmustine and the proline analog of nitrosourea caused an increase in hydrogen peroxide concentration both in fibroblasts and MCF-7 cells. Moreover, administration of carmustine and the new analog of nitrosourea caused a decrease in the activity of antioxidant enzymes. Observed changes in the antioxidant system correlated with an increase in concentration of dityrosine, as well as a decrease in tryptophan concentration. Changes in the antioxidant system were also accompanied by intensification of the lipid peroxidation process. In conclusion, carmustine and proline analog of nitrosourea produce similar changes in the antioxidant system in normal and cancer cells and are responsible for oxidative stress.
Assuntos
Antioxidantes/farmacologia , Carmustina/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Compostos de Nitrosoureia/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Prolina/análogos & derivados , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Hormonais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/tratamento farmacológico , Cálcio/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Fatores Quimiotáticos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Peróxido de Hidrogênio , Masculino , Oxirredução , Estresse Oxidativo/fisiologia , Oxigênio/metabolismo , Neoplasias da Próstata , Compostos de Sulfidrila/farmacologia , Sais de Tetrazólio/farmacologiaRESUMO
Carmustine is frequently used as anticancer drug. High toxicity and low selectivity reduces the application of this drug. Though, there is a necessity to find new compounds characterized by similar therapeutic effects but a higher selectivity and safety. As a result, the proline analogue of nitrosourea, N-[N'-(2-bromophenyl)-N'-nitrosocarbamoyl]proline (AC), has been synthesized. The aim of this study was to compare the influence of carmustine and the proline analogue of nitrosourea on the antioxidant abilities of fibroblasts and leukemia cells, MOLT4. It was shown that carmustine as well as AC cause an increase in hydrogen peroxide concentration in normal and neoplastic cells. Incubation with both compounds led to a diminution of the activity of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and reductase. Changes in activity / level of antioxidant parameters were accompanied by augmentation of lipid and oxidative protein modifications. In conclusion, carmustine and AC cause changes in the antioxidative system of normal and MOLT4 cells and are a reason of oxidative stress formation.