Resveratrol potentiates chemotherapeutic efficacy of olaparib in MCF7 human breast cancer cells by inducing apoptosis

BACKGROUND: Resveratrol is a natural polyphenolic compound found in grapes, berries, and peanuts and is well recognized for its cancer-preventive and anticancer properties. Poly(ADP-ribose) polymerase (PARP) inhibitors, such as olaparib, represent a novel class of targeted anticancer agents that impair DNA single-strand break repair, ultimately leading to genomic instability and cell death. This study aimed to investigate whether resveratrol enhances the anticancer efficacy of the PARP inhibitor olaparib in breast cancer cells. METHODS: MCF7 breast cancer cells were treated with resveratrol and olaparib, alone or in combination. Cell viability was assessed using WST- 1 and crystal-violet assays at 24, 48, 72, and 96 h to determine IC₅₀ values and combination index (CI) values. Anticancer effects were further evaluated using clonogenic survival, colony formation, and wound-healing assays. DNA damage and apoptosis were analyzed by DNA ladder assays, acridine orange/ethidium bromide (AO/EB) staining, and Western blotting. In silico analyses were performed using the Gaussian package at B3LYP, HF, and M062x levels with 6–31 g, 6–31++g, and 6–31++g(d,p) basis sets. Molecular docking against breast cancer–related proteins (PDB ID: 1A52 and 1JNX) and ADME/T property predictions were also conducted. RESULTS: Resveratrol exhibited time-dependent cytotoxicity with IC₅₀ values of 124.55 ± 4.23, 98.98 ± 4.37, 82.45 ± 1.50, and 76.86 ± 2.76 μM at 24, 48, 72, and 96 h, respectively. Olaparib IC₅₀ values were 9.60 ± 0.68, 7.08 ± 0.31, 5.24 ± 0.23, and 4.85 ± 0.26 μM at the same time points. Synergistic interactions between resveratrol and olaparib were observed at 48, 72, and 96 h, with CI values of 0.91, 0.67, and 0.62, respectively. Functional assays demonstrated that resveratrol significantly potentiated the inhibitory effects of olaparib on clonogenicity, colony formation, and cell migration. Apoptosis-related assays confirmed enhanced DNA damage and apoptotic cell death in the combination treatment group. Computational analyses supported favorable interactions of the resveratrol–olaparib combination with breast cancer–related protein targets and acceptable ADME/T properties. CONCLUSION: These findings demonstrate that resveratrol synergistically enhances the anticancer activity of olaparib by reducing cell viability, increasing DNA damage, and promoting apoptosis in MCF7 breast cancer cells. The combination of resveratrol with PARP inhibition may represent a promising therapeutic strategy for improving breast cancer treatment outcomes.