Olive leaf extracts are rich in bioactive polyphenols, including secoiridoids, phenolic acids, and flavonoids, recognized for their anticancer potential. Among various cancers, breast cancer stands out as one of the most prevalent and lethal malignancies worldwide, with high morbidity and mortality rates. Despite advancements in treatment, including surgery, chemotherapy, hormone therapy, and targeted therapies, resistance to these interventions remains a significant challenge. As a result, there is a growing interest in plant-based compounds due to their potential to enhance the current therapies or provide novel, less toxic alternatives.
This study focuses on the antiproliferative effects of three flavonoids from olive leaves due to their well-documented antioxidant, anti-inflammatory, and anticancer properties. We aimed to determine how their combinations, at various ratios, influence the inhibition of breast cancer cell growth.
Using CompuSyn software, we modeled their synergistic, additive, and antagonistic effects based on the Combination Index values. Various ratios of the three flavonoids were tested through MTT viability assays on the MCF-7 (estrogen-receptor-positive) and JIMT-1 (HER2-positive, trastuzumab-resistant) breast cancer cell lines. Additionally, an 3D isobologram was generated to visualize and confirm the nature of these interactions. The results revealed that the type of interaction depends significantly on the flavonoid ratios.
The natural ratio in olive leaf extract demonstrated strong synergy, enhancing its antiproliferative activity and confirming prior research on its efficacy against breast cancer. The optimized flavonoid ratios showed even greater synergy, suggesting that tailored combinations could surpass the previously reported results and offer a new avenue for more potent, plant-based cancer therapies.
These findings underscore the importance of refining the flavonoid ratios and exploring their molecular mechanisms to enhance polyphenol-based treatments. Further research could lead to novel therapeutic formulations that provide more effective and targeted alternatives to the conventional treatments, improving patient outcomes while reducing side effects.
