Therapeutic potential of glutathione in cancer management: a meta-analysis

Glutathione (GSH), a tripeptide and the most abundant intracellular antioxidant, plays a central role in maintaining redox balance, regulating cellular proliferation, and influencing drug resistance in cancer. Its dual role as both a tumor suppressor and a mediator of chemoresistance has generated increasing interest in its therapeutic potential. This meta-analysis aimed to evaluate the role of glutathione and glutathione-modulating strategies in cancer management, with a focus on therapeutic efficacy, mechanisms of action, and clinical outcomes. A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and Cochrane Library for studies published between 2000 and 2025. Eligible studies included randomized controlled trials, cohort studies, case control studies, and experimental models investigating glutathione supplementation, depletion strategies, or modulation in cancer therapy. Data extraction and quality assessment were performed independently by two reviewers, and findings were synthesized narratively. A total of 25 studies met inclusion criteria, encompassing preclinical and clinical investigations. Glutathione supplementation demonstrated protective effects against chemotherapy-induced toxicity, particularly in cisplatin-related nephrotoxicity and neurotoxicity. Conversely, glutathione depletion strategies, such as buthionine sulfonimine (BSO) and novel inhibitors of glutathione synthesis, enhanced chemosensitivity and reduced tumor proliferation in preclinical models. Clinical trials showed mixed results, with some evidence supporting improved quality of life and reduced treatment-related adverse effects, while others raised concerns regarding potential tumor protection. Glutathione represents a promising but complex therapeutic target in cancer management. Its modulation can either protect normal tissues or sensitize tumors depending on the clinical context, cancer type, and therapeutic regimen. Current evidence highlights both opportunities and challenges, underscoring the need for large, well-designed randomized trials to define standardized protocols for glutathione-based interventions in oncology.