Oleuropein and punicic acid induce oxidative stress and cytotoxicity in MCF-7 breast cancer cells, with protection by peroxiredoxin antioxidant proteins

BACKGROUND: Breast cancer remains a major cause of cancer-related mortality worldwide, creating a need for novel therapeutic strategies. Natural plant compounds have gained recent attention for their anticancer effects, including oleuropein from olive leaves, and punicic acid from the pomegranate fruit. In the present study, we investigated the effects of oleuropein (OL) and punicic acid (PA) on MCF-7 breast cancer cells and the role of peroxiredoxin (Prdx) antioxidants in mediating these effects. METHODS: MCF-7 cells were treated with different concentrations of OL or PA for 72 h. Viable cell density was measured by MTT assay, cytotoxicity was measured by LDH release, mitochondrial ROS was measured by MitoSOX assay, and lipid peroxidation was measured by MDA assay. The effect of Prdx suppression was determined by transient siRNA transfection, followed by cell treatments and MTT assay. RESULTS: Treatment with OL or PA produced a concentration-dependent reduction in cell viability, increased cytotoxicity, and morphological changes consistent with cellular stress and death, with PA exhibiting greater potency at lower concentrations. Both compounds significantly increased mitochondrial superoxide production, while PA also induced lipid peroxidation. Suppression of Prdx proteins increased cellular susceptibility to OL and PA treatment, with more pronounced effects following PA exposure. CONCLUSIONS: OL and PA induce oxidative stress and cytotoxicity in MCF-7 cells, and peroxiredoxins play a protective role in the cellular response. This study highlights possible efficacy of these agents for treatment, and the importance of antioxidant defense systems in subsequent cancer cell survival.