Combined Resveratrol and Curcumin Treatment Suppresses MCF-7 breast cancer cell Growth via TNF-α/NF-κB Pathway Regulation

Abstract

Abstract Background: Breast cancer remains a leading malignancy in women, with limited therapeutic options. Natural compounds such as resveratrol and curcumin exhibit anticancer properties, but their combined mechanisms are not fully understood. This study investigated the synergistic effects of resveratrol and curcumin in MCF-7 breast cancer cells. Methods: Optimal drug concentrations were determined by CCK-8 assay, followed by flow cytometry to assess apoptosis in the four treatment groups (control, curcumin, resveratrol, and combination). Transcriptome sequencing and Western blotting were performed to identify molecular mechanisms. In parallel, a network pharmacology approach was applied by integrating TNBC-related DEGs from GSE38959 with predicted drug targets, followed by KEGG and GO enrichment analysis. Results: The combination of 200 μM resveratrol and 20 μM curcumin significantly inhibited cell growth (73.60 ± 6.91% inhibition, P < 0.001 vs. control) and increased apoptosis (52.80% apoptotic cells, P < 0.001 vs. single agents). RNA-seq and enrichment analysis revealed activation of the TNF signaling pathway and modulation of the NF-κB signaling pathway in the combination treatment group. Network pharmacology further confirmed the convergence of curcumin and resveratrol targets on the TNF/NF-κB axis, which supported the transcriptomic findings. Western blot validation showed down-regulation of NF-κB, TNF-α, and c-Myc, along with up-regulation of Cleaved caspase-3(P < 0.05 for all), reinforcing the observed effects from RNA-seq and network pharmacology analysis. Conclusions: Combined resveratrol and curcumin treatment synergistically induces apoptosis in MCF-7 cells via the TNF-α/NF-κB/c-Myc axis, supporting their potential as a complementary therapy for breast cancer.

Keywords: apoptosis, breast cancer, Curcumin, MCF-7, NF-κB signaling pathway, resveratrol