Synergistic anticancer effects of zinc oxide nanoparticles and Lactococcus lactis Lysate in MCF-7 breast cancer cells: Apoptosis induction and cell cycle arrest.

BACKGROUND AND

OBJECTIVE

Breast cancer remains a major cause of cancer-related mortality, highlighting the need for novel therapeutic strategies with improved efficacy and reduced toxicity. This study aimed to evaluate the anticancer effects of zinc oxide nanoparticles (ZnO NPs), Lactococcus lactis lysate, and their combination on MCF-7 breast cancer cells, using tamoxifen as a reference treatment.

METHODS

Cytotoxicity was determined using the MTT assay. Gene expression levels of apoptotic markers (BAX, BCL2, CASP9) and cell-cycle regulators (P21, CDK4) were quantified by qRT-PCR. Treatments included ZnO NPs, L. lactis lysate, their combination, and tamoxifen.

RESULTS

ZnO NPs and L. lactis lysate exhibited IC₅₀ values of 49.7 µg/mL and 61.5 µg/mL, respectively, while their combination showed enhanced potency (IC₅₀: 31.1 µg/mL), indicating synergy. Tamoxifen exhibited an IC₅₀ of 11.7 µg/mL. Combination treatment significantly upregulated BAX (1.7-fold, p < 0.05), CASP9 (1.8-fold, p < 0.05), and P21 (1.7-fold, p < 0.05), while downregulating BCL2 (0.6-fold, p < 0.05) and CDK4 (0.5-fold, p < 0.05). These molecular changes closely mirrored tamoxifen effects (BAX: 1.8-fold; CASP9: 1.8-fold; P21: 1.8-fold; BCL2: 0.5-fold; CDK4: 0.5-fold). Mechanistically, ZnO NPs may induce oxidative stress and mitochondrial dysfunction, while L. lactis lysate may contribute through metabolic disruption.

CONCLUSION

The combination of ZnO NPs and L. lactis lysate exhibits synergistic pro-apoptotic and cell-cycle inhibitory effects on MCF-7 cells, comparable to tamoxifen. These findings support its potential as a promising complementary or alternative therapeutic strategy for breast cancer.