Selegiline, a monoamine oxidase-B inhibitor as a modulator of metabolic reprogramming for cancer therapy: a review

Metabolic reprogramming plays a crucial role in cancer progression, therapeutic resistance, and tumor-microenvironment remodelling. Monoamine oxidase-B (MAO-B), a mitochondrial enzyme involved in oxidative deamination, has recently been identified as a metabolic regulator that influences reactive oxygen species (ROS) production, mitochondrial homeostasis, and redox-dependent signaling in tumors. Selegiline, an MAO-B inhibitor traditionally used in neurological disorders, is now gaining attention for its potential role in modulating tumor metabolism. Elevated MAO-B activity contributes to oxidative stress, genomic instability, immune suppression, and metabolic adaptations that support tumor survival. By inhibiting MAO-B, selegiline reduces ROS generation, alters mitochondrial respiration, regulates glycolytic flux, and disrupts hypoxia-associated pathways, making it a promising modulator of metabolic checkpoints in oncology. Relevant literature was collected from PubMed, Google Scholar, and ScienceDirect using keywords such as Selegiline, MAO-B inhibitor, tumor metabolism, oxidative stress, and drug repurposing in cancer. Relevant studies from the past 5 years, with inclusion criteria focusing on mechanistic, preclinical, and translational evidence related to MAO-B and selegiline-mediated metabolic regulation. Recent findings indicate that selegiline not only modulates cancer cell metabolism but also influences the tumor microenvironment by reducing inflammatory cytokine production, altering macrophage polarization, and enhancing susceptibility to therapeutic stress. Additionally, combination approaches with chemotherapeutics, metabolic inhibitors, and immunotherapies show synergistic potential. This review summarizes current insights into selegiline's role in metabolic reprogramming, highlights existing challenges, and discusses future opportunities for repositioning selegiline as a targeted metabolic modulator in cancer therapy.