Synergistic effects of epoxyazadiradione (EAD) and paclitaxel against triple-negative breast cancer cells.

Abstract

Triple-negative breast cancer (TNBC) is the most aggressive and chemo-resistant form of breast cancer subtype, and chemotherapy is a vital treatment option for that. Paclitaxel is an effective chemo drug for TNBC. However, in clinical settings, paclitaxel has adverse side effects. The synergistic combination is the most promising method for overcoming undesirable toxicity and achieving a beneficial therapeutic outcome. Previous reports, including our study, showed certain anticancer potential of epoxyazadiradione (EAD), the neem limonoid, in different types of cancer cells, including TNBC. This study was designed to investigate the possible synergistic effects of EAD and paclitaxel against TNBC cells. We examined the effects of EAD and paclitaxel alone and in combination in MDA-MB 231 cells, and the percentage cytotoxicity was used to calculate synergism. Characteristic apoptotic changes were observed by visualizing cellular morphology, nuclear fragmentation and membrane integrity. We further estimated anti-migratory potential of experimental compounds by wound healing assay. The reduction in inflammation during combinatorial treatment was evaluated by observing NF-κB translocation. The combined treatment with EAD (5 μM) and paclitaxel (5 nM), which were used at doses lower than their individual IC50 concentrations, showed a synergistic effect in MDA-MB-231 cells. This combination effectively induced apoptosis and antimigration and reduced the inflammatory reactions induced by the higher dose of paclitaxel. To conclude, EAD could be the drug of choice for combined treatment with paclitaxel in a chemotherapy regimen.