Abstract 604: Punicic acid from pomegranate seed oil induces cytotoxicity and oxidative stress in MCF-7 breast cancer cells

Abstract Punicic Acid is an omega-5 long chain saturated fatty acid found in abundance in the oil of pomegranate seeds. While already known to provide various health benefits from a dietary perspective, punicic acid (PA) has also been shown to be an anti-proliferation agent in various cancer cell lines such as colorectal cancer and breast cancer. In this study, we examined the effects of PA on the MCF-7 breast cancer cell line as compared to the non-cancerous MCF-10A breast epithelial cell line. We found that PA induces dose-dependent cytotoxicity on both lines, with higher cytotoxicity in MCF-10A cells at all concentrations. MCF-7 cells exhibited relatively strong resistance to PA at the 0.4 μg/ml concentration, but increased cytotoxicity at 2 and 10 μg/ml. By contrast, there was notable cell death at all three concentrations within the non-cancerous cell line. Examination of apoptosis confirmed its role in both cell line responses to punicic acid, with significantly higher levels of apoptosis in MCF-10A cells. In order to examine the antioxidant response to punicic acid, we used qPCR to measure the expression of the Peroxiredoxin gene family (Prdx1, Prdx2, Prdx3, Prdx4, Prdx5, and Prdx6) after 48 hours of punicic acid treatment in both lines. We observed significant induction of all six Prdx genes in MCF-7 cells, with over a 4-fold increase in Prdx1, Prdx2 and Prdx6 at the 10ug/ml concentration. Interestingly, MCF-10A cells exhibited considerably higher induction of all six Prdx mRNAs at 10 μg/ml, exceeding a 30-fold induction of Prdx1, Prdx2 and Prdx5. Current work in our lab is focused on determining the role of oxidative stress in the PA-induced cytotoxicity in MCF-7 cells. Our data suggests a dose-dependent increase in mitochondrial superoxide production after 48hrs of punicic acid treatment. Analysis of other ROS markers is ongoing. Together, our data provide important new insights into the mechanisms and cell-specific effects of punicic acid, and its potential preventative and treatment efficacy in breast cancer. Citation Format: Braden Quitmeyer, Shelley A. Phelan. Punicic acid from pomegranate seed oil induces cytotoxicity and oxidative stress in MCF-7 breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 604.