Comparative evaluation of the anti-proliferative effects of alkaloid-rich extract of jujube seed and paclitaxel on MDA-MB-231 breast cancer cell line

Introduction: Cancer is the second cause of death in the world, and among all types of cancer, triple-negative breast cancer (TNBC) has one of the worst prognoses. Repeated use of chemotherapy drugs is associated with drug resistance. This study aims to investigate the effect of jujube alkaloid-rich extract on drug sensitivity and its anti-tumor effects on paclitaxel-resistant MDA-MB-231 cells in vitro. Materials and methods: The MDA-MB-231 breast cancer cell line and its paclitaxel-resistant variant were used. The XTT method was employed to measure cell viability, while Annexin-PI assays were used to detect apoptosis. Various concentrations of the jujube extract alone and in combination with paclitaxel assessed synergistic effects in 2D and 3D cell culture models. Results: The presence of alkaloids in the extract obtained from the jujube seed was confirmed by the dragendorff test and its amount was 0.395 g in 5.0 g of jujube seed powder. Paclitaxel and jujube extract exhibited dosedependent cytotoxic effects on paclitaxel-resistant MDA-MB-231 cells. The combination of jujube extract and paclitaxel significantly decreased IC50 from 541.3 mu g/mL to 124.3 mu g/mL, and the IC20 decreased from 92.1 mu g/ mL to 23.9 mu g/mL when combined with paclitaxel in 2D culture model. The combination's toxicity was reduced in the 3D culture model. Apoptosis rates were 0.75 % in the control group, 13.89 % in the alkaloid-rich extract group, 2.59 % in the paclitaxel group, and 42.90 % in the combination group. Conclusion: Combining paclitaxel with alkaloid-rich jujube seed extract enhances cytotoxicity and apoptosis in paclitaxel-resistant MDA-MB-231 breast cancer cells in both 2D and 3D culture models. This suggests that such combinations might be a viable strategy to overcome drug resistance in TNBC treatments.