The Isoflavone Formononetin Suppresses Hallmarks of Glioblastoma Progression and Activates a Compensatory Antioxidant...

To investigate the anti-glioblastoma potential of the natural isoflavone formononetin, focusing on its impact on cell survival, proliferation, migration, mediated through a potential mechanism involving oxidative stress modulation. T98G glioblastoma cells were treated with formononetin (IC₃₀ = 16.20 µM, IC₅₀ = 24.64 µM). Cytotoxicity (MTT), proliferation (trypan blue), migration (wound healing), clonogenicity (colony formation), and apoptosis (Hoechst staining) were assessed. Gene expression (qRT-PCR) of survivin, cyclin D1, Bad, MMP-9, SOD, CAT, and GPX was analyzed. Antioxidant enzyme activity and total antioxidant capacity (TAC) were measured. Formononetin dose-dependently reduced cell viability, proliferation, migration, and colony formation, while inducing apoptosis. It downregulated survivin, cyclin D1, MMP-9, and, unregulated Bad. Paradoxically, it significantly increased the activity of SOD, CAT, and GPX enzymes and enhanced TAC. Formononetin exerts potent anti-glioblastoma effects by inducing apoptosis and inhibiting key cancer hallmarks, mediated through a unique mechanism involving the paradoxical activation of the cellular antioxidant system, ultimately disrupting redox balance.