Bovine milk-derived extracellular vesicles enhance doxorubicin sensitivity in triple negative breast cancer cells by targeting metabolism and STAT signalling

Metastatic triple-negative breast cancer (TNBC) has a low 5-year survival rate of below 30% with systemic chemotherapy being the most widely used treatment. Bovine milk-derived extracellular vesicles (MEVs) have been previously demonstrated to have anti-cancer attributes. In this study, we isolated bovine MEVs from commercial milk and characterised them according to MISEV guidelines. Bovine MEVs sensitised TNBC cells to doxorubicin, resulting in reduced metabolic potential and cell-viability. Label-free quantitative proteomics of cells treated with MEVs and/or doxorubicin suggested that combinatorial treatment depleted various pro-tumorigenic interferon-inducible gene products and proteins with metabolic function, previously identified as therapeutic targets in TNBC. Combinatorial treatment also led to reduced abundance of various STAT proteins and their downstream oncogenic targets with roles in cell-cycle and apoptosis. Taken together, this study highlights the ability of bovine MEVs to sensitise TNBC cells to standard-of-care therapeutic drug doxorubicin, paving the way for novel treatment regimens.

Automated summary

In this study, bovine milk-derived extracellular vesicles (MEVs) were isolated and characterized. It was found that MEVs sensitize triple-negative breast cancer (TNBC) cells to doxorubicin, reducing their metabolic potential and cell viability. Proteomic analysis suggests that combinatorial treatment depletes pro-tumorigenic gene products and metabolic proteins, which are therapeutic targets in TNBC. The study highlights the potential of bovine MEVs to enhance the sensitivity of TNBC cells to doxorubicin and pave the way for novel treatment regimens.