Comparison of influence of carmustine and new proline analog of nitrosourea on antioxidant system in breast carcinoma cells (MCF-7)

Abstract

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.

Early Detection of Breast Cancer Using Posttranslationally Modified Biomarkers

“…Because tyrosines that are post-translationally modified by nitrating oxidants, brominating oxidants, and chloramination oxidants produced from macrophages, neutrophils or eosinophils to form nitrotyrosine, bromotyrosine and chlorotyrosine respectively, have relevance to breast cancers (26)(27)(28)(29)(30)(31)(32). For example, hypochlorous acid/hypochlorite adducts have been reported for breast cancer (33)(34)(35)(36). Our studies suggest that circulating PTM levels can be used as a biomarker for endothelial cell dysfunction, which is of concern in several human diseases.…”

Early Detection Of Breast Cancer using Post-Translationally Modified Biomarkers

“…Because tyrosines that are post-translationally modified by nitrating oxidants, brominating oxidants, and chloramination oxidants produced from macrophages, neutrophils or eosinophils to form nitrotyrosine, bromotyrosine and chlorotyrosine respectively, have relevance to breast cancers (17)(18)(19)(20)(21)(22)(23). For example, hypochlorous acid/hypochlorite adducts have been reported for breast cancer (24)(25)(26)(27). Our studies suggest that circulating PTM levels can be used as a biomarker for endothelial cell dysfunction, which is of concern in several human diseases.…”

Assessment of DNA interstrand crosslinks in NIH/3T3 cells induced by Chloroethylnitrosoureas

“…According to the clinical observation, CENUs can also lead to the generation of secondary tumors after the treatment. However, the carcinogenic mechanisms of CENUs are still poorly understood [7]. Reports showed that the pathogenetic mechanism of secondary tumors during therapy due to formation of ICLs [8].…”