Buthionine sulfoximine and chemoresistance in cancer treatments: a systematic review with meta-analysis of preclinical studies

• Published in: Journal of toxicology and environmental health. Part B, Critical reviews Vol. 26; no. 8; pp. 417 - 441
• Main Authors: dos Reis Oliveira, Camila, Pereira, Joedna Cavalcante, Barros Ibiapina, Andressa, Roseno Martins, Italo Rossi, de Castro e Sousa, João Marcelo, Ferreira, Paulo Michel Pinheiro, Carneiro da Silva, Felipe Cavalcanti
• Format: Journal Article
• Language: English
• Published: Philadelphia Taylor & Francis 17-11-2023; Taylor & Francis Ltd
• Subjects: Adjuvant treatment; Amino acids; Biosynthesis; Buthionine sulfoximine; Cancer; Cancer therapies; Carcinogens; Chemoresistance; Chemotherapy; Cytotoxicity; Drug resistance; Glutathione; Meta-analysis; oxidative damage; Platinum compounds; Reviews; Systematic review; Toxicity; Tumor cells; Tumors
• ISSN: 1093-7404; 1521-6950
• DOI: 10.1080/10937404.2023.2246876

Buthionine sulfoximine (BSO) is a synthetic amino acid that blocks the biosynthesis of reduced glutathione (GSH), an endogenous antioxidant cellular component present in tumor cells. GSH levels have been associated with tumor cell resistance to chemotherapeutic drugs and platinum compounds. Consequently, by depleting GSH, BSO enhances the cytotoxicity of chemotherapeutic agents in drug-resistant tumors. Therefore, the aim of this study was to conduct a systematic review with meta-analysis of preclinical studies utilizing BSO in cancer treatments. The systematic search was carried out using the following databases: PubMed, Web of Science, Scopus, and EMBASE up until March 20, 2023, in order to collect preclinical studies that evaluated BSO, alone or in association, as a strategy for antineoplastic therapy. One hundred nine investigations were found to assess the cytotoxic potential of BSO alone or in combination with other compounds. Twenty-one of these met the criteria for performing the meta-analysis. The evidence gathered indicated that BSO alone exhibits cytotoxic activity. However, this compound is generally used in combination with other antineoplastic strategies, mainly chemotherapy ones, to improve cytotoxicity to carcinogenic cells and treatment efficacy. Finally, this review provides important considerations regarding BSO use in cancer treatment conditions, which might optimize future studies as a potential adjuvant antineoplastic therapeutic tool.