Piperine Targets MAOB and Enhances Temozolomide-induced Cytotoxicity in Glioblastoma Cell Lines

Background/Aim: Glioblastoma (GBM) is a highly aggressive brain tumor with limited treatment options due to its aggressive nature, high recurrence rate, and resistance to conventional therapies. Piperine, a bioactive compound in black pepper, crosses the blood-brain barrier (BBB) and exhibits anti-cancer effects. This study investigates the mechanism of action of piperine in GBM, particularly its interaction with monoamine oxidase B (MAOB) and synergy with temozolomide (TMZ).

Materials and Methods: Molecular docking analysis identified MAOB as a target of piperine. Western blot and gene expression analyses assessed MAOB levels in U373 and Hs683 glioblastoma cell lines. Cell viability, reactive oxygen species (ROS) levels, and DNA damage markers were evaluated to determine the cytotoxic effects of piperine, alone and in combination with TMZ.

Results: MAOB is significantly overexpressed in GBM and correlated with poor patient prognosis. Piperine effectively down-regulated MAOB, induced selective cytotoxicity in glioma cells, modulated oxidative stress via NRF2 up-regulation, and enhanced DNA damage response. Co-treatment with piperine and TMZ significantly enhanced cytotoxicity and DNA damage.

Conclusion: Piperine exerts anti-GBM effects by targeting MAOB, disrupting ROS homeostasis, and inducing DNA damage. It also enhances TMZ efficacy, highlighting its potential as an adjuvant therapy for GBM.