Synergistic anticancer effect of ellagic acid and Kaempferol combination in a mouse model of breast cancer

Background Cancer continues to be a major global health issue and is one of the leading causes of death. Breast cancer ranks among the most common neoplasms worldwide. Natural products have shown notable advantages in cancer treatment. Ellagic acid (EA), a polyphenolic compound found in natural sources, has potent anticancer properties. Kaempferol (KAE) is a natural substance known for its strong anticancer activity. This study investigated the antitumor activity of the combined use of EA and KAE on various cancer cell lines. Methods In vitro , EA, KAE, and their combination were evaluated for their antiproliferative activity against five cancer cell lines: MDA-MB-231, T47-D, HeLa, EMT-6/P, A549, as well as the non-cancerous Vero cell line. The impact of each treatment on cell viability was examined using the MTT assay. T47-D cells were treated with EA, KAE, and a combination of both, and caspase-3 activity was measured. For the in vivo study, EMT-6/P cells were injected into Balb/C mice, which were treated with EA, KAE, and their combination. Tumor size and weight were measured, and hepatotoxicity and nephrotoxicity were also investigated for all treatments. Results In vitro , the combination of EA and KAE exerted a synergistic antiproliferative effect across all tested cancer cell lines, with the most pronounced effect observed in T47-D cells. This combination produced low toxicity in the non-cancerous Vero cell line. Furthermore, the combination led to a greater induction of apoptosis compared to single-agent treatment. In vivo , the EA and KAE combination exhibited a notable reduction in tumor volume (p< 0.05) and increased proportion of tumor-free mice. Safety evaluations showed no signs of liver or kidney toxicity in the combination-treated group (p > 0.05). Conclusion The combination of EA and KAE represents a promising candidate for breast cancer treatment due to its synergistic effect. It maximizes therapeutic potential through the induction of apoptosis.