Integration of multiomics reveals the mechanism of Lycium barbarum polysaccharides inhibit MCF-7 cell proliferation

Background：Breast cancer, as a highly prevalent malignant tumor among women, has a consistently high mortality rate due to metastasis and drug resistance. Lycium barbarum polysaccharides (LBP), which have been reported to have significant anti-tumor activity, have not yet had their molecular mechanism and signaling pathways against breast cancer clearly defined. Methods and Results：In this study, the CCK-8 assay determined that treatment with 8 mg/mL LBP for 48 h was the optimal condition for subsequent multi-omics analysis. The results demonstrated that a high concentration of LBP significantly reduced the viability of MCF-7 cells and inhibited cell proliferation. Transcriptome sequencing revealed that LBP markedly altered the expression levels of the genes HO-1, FTH1, FTL, and TFRC. Metabolomics analysis further indicated that LBP significantly impacted glutathione metabolism, glycerophospholipid metabolism, and the alanine-aspartate-glutamate metabolic pathway. Further integration of transcriptomic and metabolomic data suggests that LBP may suppress cell proliferation by activating the ferroptosis pathway via the NRF2/HO-1 axis. To further validate this hypothesis, we conducted additional experiments to detect the NRF2/HO-1 signaling pathway and markers associated with ferroptosis. The results demonstrated that LBP treatment significantly upregulated the expression of NRF2 and its downstream effector molecule HO-1. Moreover, the specific NRF2 inhibitor ML385 was able to reverse the alterations in GSH, Fe2+, and MDA levels induced by LBP. Conclusion：In conclusion, our research results indicate that LBP induces ferroptosis by activating the NRF2/HO-1 signaling pathway.