The search for NF-κB blockers to optimize antioxidants and counteract inflammation and carcinogenesis has identified several promising natural compounds, encompassing curcumin. Nonetheless, despite the pleiotropic health attributes of curcumin and established safety, its in vivo efficacy is limited by its poor pharmacokinetic properties, primarily due to its low bioavailability because of its low free serum concentrations and short half-life. To overcome these restrictions, we investigated the efficacy of the synthetic curcumin analog PAC in breast cancer cells. Additionally, MCF-7 and MDA-MB-231 cell lines were employed to explore the anticancer effects of PAC by assessing cell viability, apoptosis, clonogenic survival, and the expression of NF-κB, p53, Bcl-2, and Bax. Our results validate that PAC effectively inhibits cell proliferation and induces apoptosis in a dose-dependent manner. PAC also significantly enhances the radiosensitivity of breast cancer cells, indicating a potential synergistic effect with radiation therapy. Mechanistically, PAC exerts anticancer effects by inhibiting NF-κB signaling and modulating apoptotic genes like p53, Bax, and Bcl-2. These findings highlight its potential as a breast cancer therapeutic, enhancing existing treatments.