Fingerroot-derived nanovesicles attenuate atypical teratoid rhabdoid tumor progression via modulation of Wnt signaling

Atypical teratoid rhabdoid tumor (ATRT) is an aggressive central nervous system tumor that primarily affects young children and has poor prognosis, highlighting the need for new treatment options. In this study, we examined how fingerroot exosome-like nanovesicles (FELNs) derived from Boesenbergia rotunda (L.) Mansf. affect ATRT and investigated their mechanisms of action. FELNs are round vesicles approximately 100 nm in diameter. Fluorescently labeled FELNs were taken up by cells and induced dose- and time-dependent cytotoxicity via apoptosis in ATRT cell lines BT12 and cisplatin-resistant BT16, with minimal effect in normal brain cells. Moreover, non-toxic concentrations of FELNs significantly decreased ATRT cell migration and invasion. Proteomic analysis revealed that FELNs disrupt multiple signaling pathways involved in ATRT development, including the Wnt/β-catenin pathway. FELN treatment reduced β-catenin protein levels and increased GSK-3β activity. It also decreased the expression of target genes, including c-myc, cyclin D1, axin2, and survivin . Overall, our findings demonstrate that FELNs exert anti-cancer effects in ATRT cells by inducing apoptosis and decreasing migration and invasion. These effects are partially mediated through the GSK-3β-dependent β-catenin pathway. The low toxicity in normal cells suggests that FELNs could be promising new therapeutic agents for cancer treatment.