Adverse effect of Tamarindus indica and tamoxifen combination on redox balance and genotoxicity of breast cancer cell.

Abstract

Background: Breast cancer is the most significant threat to women worldwide. Most chemotherapeutic drugs cause cancer cell death and apoptosis by inducing oxidative stress and producing reactive oxygen species (ROS). Cancer cells have a higher rate of metabolic activity than normal cells and thus produce more ROS. Glutathione and its related enzymes are the most significant antioxidant defense mechanisms that protect cells from oxidative and chemotherapeutic impacts. The anticancer actions of phenolic compounds were greatly confirmed. Using phenolic compounds as drugs in combination with chemotherapy may improve health, improve treatment outcomes, and reduce dose and damage. The goal of the study was to treat breast cancer cell lines (MCF-7) with Tamarindus indica extract individually and in combination with the anticancer drug tamoxifen (TAM) to improve therapeutic efficacy.

Results: After 48 h of incubation at IC₂₅ concentrations of T. indica extract (47.3 g/mL), tamoxifen (0.8 g/mL), and their co-treatments, the biochemical and genotoxic effects on MCF-7 cell lines were investigated. In MCF7 cell lines, T. indica extract increased reduced glutathione levels as well as glutathione transferase, glutathione peroxidase, and glutathione reductase activities. The same was true for oxidative state indicators, where higher levels of catalase and lactate dehydrogenase activity were associated with higher levels of malondialdehyde. T. indica has almost no effect on the DNA damage parameters. All of these variations can produce alterations in cancer cell genotoxicity and apoptotic pathways, explaining the restoration of DNA moment to normal levels and enhanced survival.

Conclusion: Cytotoxic and genotoxic effect of treatment with T. indica extract could be attributed to the dynamic interaction of glutathione cycle and antioxidant enzymes to combat oxidative stress, which can be considered as a positive therapeutic effect. On the other hand, the negative response of tamoxifen efficacy when co-treated with T. indica reversed tamoxifen's genotoxicity and enhanced survival.