Objective: Breast cancer is the most common type of cancer and is one of the leading cancer-related deaths in women. With the recognition that they are the leading tumor cells responsible for tumor development, resistance to treatment, and post-treatment tumor recurrence, recent studies has focused on cancer stem cell-targeted cellular therapies. Alpha lipoic acid (ALA), a naturally occurring disulfide molecule; is a potent antioxidant that has been shown to provide beneficial effects on cell proliferation and apoptosis in a variety of cancer cell lines. Mesenchymal Stem Cells (MSCs) are multipotent adult stem cells and exist on many tissues. There are conflicting studies suggesting that MSCs inhibit or promote cancer development and progression. It is known that the paracrine effects of MSCs are mediated by exosomes. In this study, the effects of ALA-stimulated MSC exosomes as nano-sized biocarriers on proliferation, apoptosis and migration processes in breast cancer stem cells (BCSCs) were investigated. Method: Isolation and characterization of BCSCs and human adipose derived mesenchymal stem cell (hAT-MSC) was performed. hAT-MSCs were stimulated by culturing with ALA for two passages. hAT-MSC and hAT-MSC-ALA exosomes isolated by ultracentrifugation method and protein quantification performed. BCSCs's; direct culture with ALA supplement, ALA- stimulated MSC exosomes and additionally indirect co-culture with MSCs were performed. Differences in proliferation, apoptosis and migration between groups; demonstrated by quantitative real-time PCR (Q-PCR), ELISA, migration assay, annexin V/PI, WST-1, and immunofluorescent staining. Results/Conclusion: ALA-stimulated MSC exosomes did not have a statistically significant effect on the apoptosis and proliferation processes of BCSCs, but it was observed to increase migration. Among the groups, only the 3mM ALA group selected as the toxic dose showed a significant increase in the apoptosis level of BCSCs.

Keywords: Breast Cancer, Cancer Stem Cell, Mesenchymal Stem Cell, Alpha Lipoic Acid, Exosome