Enhanced Apoptotic Effects in MDA-MB-231 Triple-Negative Breast Cancer Cells Through a Synergistic Action of Luteolin and Paclitaxel

Background and aim: According to reports on cancer incidence in 2020, breast cancer became the leading malignancy among women worldwide. This multistep disease involves genetic and environmental factors. Paclitaxel, a naturally occurring antimitotic substance, is a widely used chemotherapeutic drug for treating various human malignancies, including breast cancer. However, its major drawback is its extensive toxicity. This limitation can be mitigated through combination therapy with natural products like luteolin. Studies suggest that luteolin has anticancer properties, as it inhibits cancer cell growth and induces apoptosis in breast, lung, and colon cancers. This study aims to investigate the synergistic anticancer effects of combining luteolin and paclitaxel on breast cancer cells.

Methods: Breast cancer cell line (MDA-MB-231) was utilized for this study. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was then conducted to check the cell viability. This was followed by a morphology study conducted under a phase contrast microscope. Morphological analysis revealed pronounced cell shrinkage and membrane blebbing, indicative of apoptosis when treated with the combination at their IC50 values. Gene expression results further confirmed the anticancer properties by showing significant downregulation of the B-cell lymphoma-2 (BCL-2) anti-apoptotic gene. These findings suggest that the luteolin-paclitaxel combination exerts a synergistic effect, enhancing anticancer activity in breast cancer cells. Reverse transcriptase polymerase chain reaction (RT-PCR) was done to analyze the genes involved in apoptosis. Finally, the data collected was statistically analyzed to confirm the reliability of the study.

Results: The combination of 1 μM/ml of paclitaxel and increasing concentrations of luteolin showed a great percentage of reduction in cell viability and the IC50 value of luteolin concentration was around 40 μM/ml. The morphology study revealed that the cancer cells showed shrinkage and blebbing on treatment with 40 μM/ml. At the same IC50 concentration, the combination of luteolin and paclitaxel resulted in a significant downregulation of BCL-2 mRNA expression in breast cancer cells compared to luteolin alone.

Conclusion: The combination of paclitaxel and luteolin has a synergistic effect on breast cancer cells and shows potential as a treatment for various cancers. Given these promising results, the paclitaxel and luteolin combination could be developed into a potent therapeutic strategy for treating various cancers. Future research should include in vivo studies to further assess the therapeutic potential and safety profile of this combination.