<em>Lentinula edodes </em>Cultured Extract Treated Mesenchymal-Derived Extracellular Vesicle Modulated Breast Cancer Stem Cells and Reprogramming of microRNAs

Background: Breast carcinoma represents the most frequent malignancy in women in Canada. The intrinsic or acquired drug resistance significantly contributes to in-creased risk of recurrence and metastasis. Although, front-line therapy is multimodal, chemoresistance remains a major hurdle in treatment and therapy. Intake of natural compounds issued from the fermentation processes are now considered a god strategy to help overcome chemoresistance. Materials and Methods: Extracellular vehicles (EVs) from Mesenchymal Stro-mal/Stem Cells (MSCs) pretreated with Lentinula edodes cultured extract (AHCC) were used to study the effect on reducing chemoresistance and modulating mi-croRNAs in cell lines, MCF-7 and MCF-7/DOX cells by EVs derived from MSCs under AHCC treatment. Characterization of EVs was done by using nanoparticles tracking analysis. MicroRNas and the formation of cancer stem cells were studied. Results: miRNA analysis revealed that AHCC remarkably affected the expression of several microRNAs, amongst which are miR-155, miR-34a, miR-Let7 and miR-200c. In vitro experiments showed inhibition of cancer stem cell proliferation after challenging the cells with EVs pretreated with AHCC. Conclusion: Our data demonstrated that AHCC may contribute to the modulation of tumor microenvironment, thus influenc-ing the development of cancer stem cells.