Preferential toxicodynamic effects of fenbendazole in ovarian cancer and nonmalignant ovarian cell models

Ovarian cancer remains a major cause of death among gynecologic malignancies because of late diagnosis, frequent recurrence, and resistance to standard chemotherapy. Drug repurposing offers a cost-effective strategy for identifying alternative therapeutic agents, but the comparative toxicodynamic effects of fenbendazole in malignant and nonmalignant ovarian cell models remain incompletely characterized. In this study, the toxicodynamic effects of fenbendazole were evaluated in malignant ovarian cell lines (OVCAR8 and A2780) and compared with those in a nonmalignant ovarian epithelial comparator (IOSE-80) using integrated in vitro approaches, with exploratory in silico analysis as supportive structural context. Fenbendazole reduced viability in ovarian cancer cells in a time- and concentration-dependent manner. At 72 h, IC50 values were lowest in A2780, intermediate in OVCAR8, and remained above the tested concentration range in IOSE-80, yielding lower-bound selectivity indices in favor of malignant cells. Fenbendazole also increased G2/M accumulation, γ-H2AX and cleaved caspase-3 signals, and Annexin V-positive cell populations in malignant cells. These findings indicate that fenbendazole exerts preferential toxicodynamic effects in malignant ovarian cell models relative to the nonmalignant comparator used in this study. An exploratory molecular docking analysis provided limited supportive structural context for a possible tubulin-related mechanism but was not interpreted as evidence of direct target engagement.