CYTOTOXIC EFFECT OF OXYRESVERATROL ON MURINE BREAST CANCER CELLS UNDER NORMOXIA AND HYPOXIA CONDITIONS

INTRODUCTION AND OBJECTIVES: In the last decade breast cancer is a pathology with highly prevalence worldwide. Hypoxia is present in solid tumors, mainly due to disordered cell growth and abnormal vascularization. Natural compounds have shown promise in preventing tumor development while exhibiting reduced toxicity to healthy cells compared to conventional treatments. Oxyresveratrol (ORV) is a phytochemical found in blackberries with diverse biological properties. However, its specific effects on breast cancer, especially in hypoxia remain unexplored. The aim of this study was to analyze the cytotoxic effect of ORV in murine breast cancer cells and their response after exposure to induced hypoxias. MATERIAL AND METHODS: Cells viability was evaluated by MTT method. The cell cycle phases and type of cell death were analyzed by flow cytometry after labeling with RNAse-PI or annexin-V-FITC-PI. The hypoxic condition was induced by cobalt chloride (CoCl₂). The mitochondrial membrane potential (ΔΨm) and the detection of reactive oxygen species (ROS) were analyzed by flow cytometry after labeled the cells with JC-1 and DCFDA, respectively. Protein levels was evaluated by Western blotting. Data were analyzed using Student’s t-test when comparing two groups or one-way ANOVA for more than two groups using the software GraphPad Prism 6.0. RESULTS AND CONCLUSION: ORV presented cytotoxicity effect in 67NR cells under normoxia, acute hypoxia and chronic hypoxia with IC₅₀ of 118.40, 49.66 and 80.53 µM, respectively. ORV decreases the ROS production in normoxia and alter the Δᴪm. Cell cycle phases (G0/G1) were altered after ORV treatment in both conditions and lead the cells to apoptosis. ORV reduced 1.28-times the levels of HIF-1α in chronic hypoxia. In summary, we observed the effect of ORV in normoxia and a better effect in an environment of acute hypoxia, which leads us to suggest them as promising candidates for future in vivo trials with anticancer properties.