Kim Hyeon Ji, Shin Chang-Hoon, Kim Tae-Jun, Kim DO-Yeon
Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea.
Preclinical Research Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Republic of Korea.
Anticancer Res. 2025 Jul;45(7):3009-3020. doi: 10.21873/anticanres.17666.
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).
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.
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 NRF2 up-regulation, and enhanced DNA damage response. Co-treatment with piperine and TMZ significantly enhanced cytotoxicity and DNA damage.
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.
背景/目的：胶质母细胞瘤（GBM）是一种侵袭性很强的脑肿瘤，由于其侵袭性、高复发率以及对传统疗法的耐药性，治疗选择有限。胡椒碱是黑胡椒中的一种生物活性化合物，可穿过血脑屏障（BBB）并具有抗癌作用。本研究探讨胡椒碱在GBM中的作用机制，特别是其与单胺氧化酶B（MAOB）的相互作用以及与替莫唑胺（TMZ）的协同作用。
分子对接分析确定MAOB为胡椒碱的靶点。蛋白质印迹法和基因表达分析评估了U373和Hs683胶质母细胞瘤细胞系中MAOB的水平。评估细胞活力、活性氧（ROS）水平和DNA损伤标志物，以确定胡椒碱单独及与TMZ联合使用时的细胞毒性作用。
MAOB在GBM中显著过表达，且与患者预后不良相关。胡椒碱有效下调MAOB，在胶质瘤细胞中诱导选择性细胞毒性，调节氧化应激并上调NRF2，增强DNA损伤反应。胡椒碱与TMZ联合治疗显著增强细胞毒性和DNA损伤。
胡椒碱通过靶向MAOB、破坏ROS稳态和诱导DNA损伤发挥抗GBM作用。它还增强了TMZ的疗效，突出了其作为GBM辅助治疗的潜力。
