Impact of hyperglycemia on glioblastoma cell proliferation and the therapeutic potential of green-synthesized cerium oxide nanoparticles
摘要
Diabetes mellitus (DM) is a major metabolic disorder that promotes cancer progression, including in glioblastoma cells. Persistent hyperglycemia alters the tumor microenvironment, increasing cell proliferation and disturbing oxidative balance. However, the molecular mechanisms connecting high-glucose levels to glioblastoma growth are not fully understood, and the role of redox-active nanomaterials in regulating this effect has not been thoroughly investigated. Therefore, this study investigated the effects of normoglycemic (i.e., at 5 mM) and hyperglycemic (i.e., at 10 and 25 mM) conditions on U87 glioblastoma cells at 24, 48, and 72 h, followed by treatment with Mentha-derived green-synthesized cerium oxide nanoparticles (CeO2 NPs) at different concentrations ranging from 62.5 to 1000 µg/mL. The results demonstrated that Mentha royleana based CeO2 NPs showed pronounced cytotoxicity across all glucose conditions, with significant apoptosis observed particularly at 25 mM of glucose. At 24 h, CeO2NPsM.A exhibited the lowest cell viability (16%) at 1000 µg/mL, with 22% viability at 10 mM and 57% at 25 mM glucose. At 48 h, viability was reduced to 50% and 48% at 5 mM and 10 mM glucose, respectively, while at 72 h, viability further declined to 45% and 40%. The CeO2NPsM.L have shown efficient nuclear apoptosis and nuclear membrane breakage with cells appearing star shaped. Overall, treatment with CeO2 NPs elicited potent cytotoxic effects, including mitochondrial membrane depolarization, suppressed myofibroblast formation, and enhanced reactive oxygen species (ROS) generation. The study concluded that hyperglycemia promotes glioblastoma proliferation, whereas green-synthesized CeO2 NPs mitigate this effect by inducing redox-mediated mitochondrial and nuclear damage. This study highlights the potential of biogenic CeO2 NPs as multifunctional nanotherapeutic agents capable of targeting glucose-dependent metabolic vulnerabilities in glioblastoma.
Graphical Abstract