Momordica charantia-derived extracellular vesicles-like nanovesicles inhibited glioma proliferation, migration, and invasion by regulating the PI3K/AKT signaling pathway

Abstract

• MCELNs were similar to animal cell-derived extracellular vesicles. • MCELNs penetrated the BBB. • MCELNs inhibited glioma growth via reguating PI3K/AKT pathway. • MCELNs suppressed metastasis via downregulating MMP9. Momordica.charantia has antioxidant and neuroprotective effects, but its anti-glioma capacity remains unclear. Plant-derived nanovesicles have shown therapeutic potential in inflammation and cancer. This study explored the therapeutic effects of Momordica.charantia -derived extracellular vesicles-like nanovesicles (MCELNs) in treating glioma and its underlying mechanisms. The MCELNs were successfully isolated and characterized similarly to animal cell-derived extracellular vesicles. The in vitro assays identified that MCELNs inhibited the proliferation but did not promote apoptosis of U251 glioma cells. MCELNs repressed U251 glioma cells migration and invasion via proceeding the epithelial-mesenchymal transition process and downregulating MMP9. MCELNs penetrated the BBB and suppressed the glioma growth and metastasis in vivo . The ratios of p-AKT/AKT and p-PI3K/PI3K were downregulated in MCELNs treated U251 glioma cells compared with the control. Highly expressed miR5813 in MCELNs might be involved in the PI3K/AKT pathway that needs further investigation. MCELNs could serve as a novel therapeutic strategy for glioma treatment.