Baicalein Sensitizes Triple Negative Breast Cancer Cells to Cisplatin by Activating Apoptosis

Objective/background The potential for natural products to work synergistically with chemotherapy to reduce side effects and enhance its effectiveness has garnered significant attention. This study aims to evaluate the potential synergistic effect of baicalein, a flavone, in enhancing the chemosensitivity of cisplatin in the MDA-MB-231 triple-negative breast cancer cell line. Methods The impact of baicalein-cisplatin combination on cytotoxicity, migration, colony formation, and apoptosis was investigated. Results Baicalein exhibited a cytotoxic effect against the MDA-MB-231 cell line, with an IC 50 of 44 µM, whereas cisplatin demonstrated an IC 50 of 3.5 µM. Cells treated with cisplatin-baicalein combination at 1:4 ratio demonstrated increased sensitivity to cisplatin, showing a twofold reduction in the IC 50 . Notably, reductions of 7.23, 12.99, 23.37, and 34.84-fold in the ED 50, ED 75, ED 90 , ED 95 , respectively of cisplatin against MDA-MB-231 cells were observed in the baicalein-cisplatin combinations. The combination of 1.5 µM of cisplatin with 6 µM of baicalein resulted in a significant reduction in the number of colonies compared to 1.5 µM of cisplatin alone ( p < .05). Baicalein failed to enhance the anti-migratory effect of cisplatin at all studied combinations after 72 h in comparison with cisplatin alone. Baicalein (6 and 3 µM) and cisplatin (3 µM) increased CASP3 while baicalein (6 and 3 µM) and cisplatin (3, 1.5 µM) decreased BCL2 gene expression in MDA-MB-231 cells. Their combinations were not significantly different from the corresponding concentration of cisplatin alone. Conclusion This study demonstrated for the first time that baicalein enhances the cytotoxicity of cisplatin in MDA-MB-231 cells by increasing apoptosis, lowering cisplatin's IC 50 and inhibiting colony formation. This synergy may reduce the required doses and side effects, supporting baicalein's potential as a chemotherapy adjuvant.