Punicalagin Inhibits the Growth and Proliferation of Ovarian Epithelial Adenocarcinoma Cells Via Apoptosis and Autophagic Cell Death

ABSTRACT Ovarian cancer remains a leading cause of gynecologic cancer‐related mortality and is frequently associated with therapeutic resistance. Punicalagin (PCG), a pomegranate‐derived polyphenol, has demonstrated anticancer activity in multiple tumor models, however, its effects in ovarian cancer require further clarification. This study evaluated the anti‐proliferative and anti‐migratory effects of PCG in two biologically distinct ovarian cancer cell lines, OVCAR‐3 and SKOV‐3. PCG treatment (6.25–200 µM) significantly reduced cell viability and colony formation in a dose‐ and time‐dependent manner. Migration‐associated behaviors were suppressed in wound‐healing and transwell assays, accompanied by modulation of epithelial–mesenchymal transition markers, including increased E‐cadherin and decreased N‐cadherin expression. PCG increased reactive oxygen species (ROS) levels and reduced mitochondrial membrane potential in both cell lines. Annexin V/propidium iodide analysis demonstrated increased apoptotic cell populations, with elevated BAX expression. Autophagy‐related changes, including LC3‐I to LC3‐II conversion and acridine orange–positive vesicles, were observed in OVCAR‐3 cells but not in SKOV‐3 cells. Collectively, these findings indicate that PCG exerts anti‐proliferative and pro‐apoptotic effects in ovarian cancer cells and is associated with oxidative stress and mitochondrial dysfunction. Further studies are required to define the mechanistic contribution of ROS and autophagy and to evaluate translational relevance in vivo.