Alkaloid-rich extract of jujube seed regenerate the antiproliferative effect of paclitaxel on paclitaxel-resistant MDA-MB-231 breast cancer cell line in 2D and 3D cultures

Abstract

Introduction: Cancer is the second leading cause of death globally, and among all types of cancer, triple-negative breast cancer (TNBC) has one of the worst prognoses. The repeated use of chemotherapeutic drugs often leads to drug resistance, complicating treatment outcomes. This study aimed to investigate the effect of jujube alkaloid-rich extract on drug sensitivity and its antitumor effects on paclitaxel-resistant MDA-MB-231 cells in vitro. Materials and methods: This study utilized the MDA-MB-231 breast cancer cell line and its paclitaxel-resistant variant. Cell viability was measured using the XTT assay, while apoptosis was detected through Annexin-PI assays. Various concentrations of jujube extract, alone and combined with paclitaxel, were assessed for synergistic effects in 2D and 3D culture models. Results: The presence of alkaloids in the jujube seed extract was confirmed via the Dragendorff test, with 0.395 g of alkaloids present in 5 g of jujube seed powder. A combination of paclitaxel and jujube extract exhibited dose-dependent cytotoxic effects on paclitaxel-resistant MDA-MB-231 cells. The combination of jujube extract and paclitaxel significantly decreased IC50 from 541.3 μg/ml to 124.3 μg/ml, and the IC20 decreased from 92.1 μg/ml to 23.9 μg/ml when combined with paclitaxel in 2D culture model. The cytotoxicity of the combination 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 alkaloid-rich jujube seed extract with paclitaxel regenerates the cytotoxicity and apoptotic ability of paclitaxel in the 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.

Keywords

• Alkaloid-rich extract
• Breast cancer
• Ziziphus Jujuba
• MDA-MB-231 Cell line
• Paclitaxel