Menstrual Blood Stem Cell-Derived Exosomes as Modulators of Apoptosis, Migration and Angiogenesis in Breast Cancer...

The complexity of breast cancer cells complicates the process of enhancing our understanding, which may lead to the development of effective therapeutic agents and approaches. Among the novel medical interventions, menstrual blood-derived mesenchymal stem cells (Mens-MSCs) demonstrate proactive and immunomodulatory interactions with malignant cells. This study aims to evaluate the effects of Mens-MSCs-derived exosomes (MM-Exos) on breast cancer cell behaviors, with particular emphasis on apoptosis, migration, and angiogenesis. MM-Exos were characterized using DLS, flow cytometry, and TEM. After determining the effective concentration by MTT assay, the exosomes were applied to MDA-MB-231 and SK-BR-3 cell lines. Cell motility was evaluated using a scratch assay, while apoptosis, cell cycle distribution, and ROS generation were assessed by flow cytometry and ELISA. Gene expression of BAX, BCL-2, MMP-2, and VEGF was analyzed by qPCR, and corresponding protein levels were confirmed through Western blotting. Based on the results, MM-Exos dose-dependently decreased breast cancer cell survival across both cell lines. Furthermore, MM-Exos at 50 and 100 µg/ml significantly reduced the migratory rate of cell lines (P < 0.001). Treatment with MM-Exos (100 µg/ml) significantly increased ROS production (P < 0.001), enhanced apoptosis (P < 0.001), induced cell cycle arrest (P < 0.001), and altered gene and protein expression. Both cell lines exhibited significant down-regulation of VEGF(P < 0.001), BCL-2 (P < 0.01), and MMP-2 (P < 0.01) after treatment with MM-Exos, whereas BAX demonstrated significant up-regulation (P < 0.001). Based on results, MM-Exo demonstrates anticancer functions by enhancing cytotoxicity, ROS generation, apoptosis, while reducing migration rate. Thus, MM-Exo may represent a potential therapeutic option for breast cancer; however, further comprehensive studies are required.