Illuminating the pleiotropic effects of bixin-loaded nanoemulsion on glioblastoma cell behavior through an integrated approach.

backgroundGlioblastoma is a pervasive brain cancer characterized by extreme aggressiveness and death rates. The high fatality rate of GBM is accentuating the need for efficient natural alternatives, such as bixin. Bixin is an apocarotenoid abundant in Bixa orellana L. Despite its prominent coloring potential, the structural distinctiveness and remarkable antioxidant potential confer bixin therapeutic efficacy in ameliorating cancers in experimental models. Therefore, the present study developed a bixin-loaded nanoemulsion (BNE) to investigate the pleiotropic effects of bixin on GBM. METHODS AND

resultsAn integrated approach comprising in-vitro and in-silico analyses was adopted to elucidate the pharmaceutical potential of bixin in targeting key signaling molecules involved in proliferation, migration, and invasion. Interestingly, BNE suppressed the proliferation of GB cells in a concentration-dependent manner. Furthermore, BNE curbed the invasion and migration of Ln-229 cells, as evidenced in migration and invasion assays. BNE downregulated the expression of cortactin, a key protein involved in the invadopodia formation for the motility of GBM cells. The western blot analysis substantiated that BNE acts on PTEN/PI3K/AKT signaling and the ERK1/2 pathway to impede the proliferation of Ln-229 cells. Moreover, BNE curtailed the migration and invasion of Ln-229 cells by targeting FAK/Src signaling and by downregulating MMP9 expression. In silico analysis, including docking studies and molecular dynamics simulations, further corroborated the interaction of selected target proteins with bixin.

conclusionTaking together, our findings revealed that bixin has therapeutic potential in mitigating GBM cell behavior by acting on multiple targets to limit its proliferation, migration, and invasion.