Bovine milk-derived extracellular vesicles enhance doxorubicin sensitivity in triple negative breast cancer

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. Researchers at La Trobe University 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.

Proteomic analysis with heatmaps and gene enrichment analysis suggested that MEVs in combination with doxorubicin impaired metabolic potential of cells

(A) Heatmap representing proteins that are 2-fold differentially abundant in MEV and doxorubicin treated cells as compared to WT cells. Gene enrichment analysis was performed using FunRich to compare differential abundance of proteins involved in various biological processes when cells were subjected to combinatorial treatment versus (B) WT cells, (C) MEV treated cells, (D) Doxorubicin treated cells. Significance is determined by hypergeometric test.