Bacoside-A enhances temozolomide-induced cytotoxicity in U87MG glioblastoma cells via ROS-mediated apoptosis and EGFR/MAPK inhibition.

Temozolomide (TMZ) is the primary chemotherapeutic agent for glioblastoma multiforme (GBM), but its effectiveness is limited by resistance, recurrence, and toxicity. Combining natural compounds with TMZ is a promising approach to overcome these challenges. Bacoside-A, a brain tonic derived from Bacopa monnieri with proven anticancer properties, was evaluated for its chemotherapeutic potential in U87MG cells. Our study demonstrates that the combination of Bacoside-A and TMZ significantly enhanced intracellular TMZ accumulation and promoted ROS-mediated apoptosis through Ca2+ influx, mitochondrial membrane depolarization, and subsequent cell death by Apoptosis. Additionally, inhibition of EGFR-driven MAPK signalling and suppression of NF-κB nuclear translocation were observed, highlighting modulation of key survival pathways. These findings suggest that Bacoside-A potentiates TMZ efficacy while enabling dose reduction, thereby minimizing toxicity. Overall, this combinatorial approach provides mechanistic insights and a potential therapeutic strategy for improving GBM treatment outcomes.