Metabolic Reprogramming Triggered by Fluoride in U-87 Glioblastoma Cells: Implications for Tumor Progression?

Chronic inflammation is a hallmark of brain tumors, especially gliomas, which exhibit elevated levels of pro-inflammatory mediators within the tumor and its microenvironment. Metabolic disturbances triggered by fluoride as a pro-oxidative agent in glioma cells, known for their high aggressiveness and resistance to therapy-remain poorly understood. Therefore, investigating the impact of physiologically elevated fluoride concentrations on oxidative stress and pro-inflammatory responses in glioma cells represents a relevant and timely research objective.

U-87 human glioblastoma cells were subjected to short-term and long-term exposure to physiologically high concentrations of NaF (0.1-10 µM). Both the cells and the culture medium were analyzed. We assessed levels of reactive oxygen species (ROS), antioxidant defenses, and a panel of cytokines and chemokines.

Our results demonstrated that oxidative stress and inflammatory conditions in U-87 cells varied with fluoride concentration and exposure time. This led to an increase in ROS levels and key pro-inflammatory cytokines, including IL-6 and TNF-α.

Fluoride compounds can generate ROS and disrupt the antioxidant defense system in U-87 human glioblastoma cells, leading to the initiation and progression of inflammatory states. Furthermore, prolonged exposure to NaF may induce adaptive mechanisms in U-87 cells.