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ABSTRACT
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.
Acknowledgments
We wish to thank the public Brazilian agency “Fundação de Amparo à Pesquisa do Estado do Piauí” (FAPEPI, Teresina, Brazil) in the form of scholarships for Joedna Cavalcante Pereira. Dr Paulo Michel Pinheiro Ferreira is also grateful to the “Conselho Nacional de Desenvolvimento Científico e Tecnológico” for his personal scholarship (CNPq #304803/2022-7).
Disclosure statement
No potential conflict of interest was reported by the author(s).
Authorship contributions
CRO and JCP: Conceptualization, Methodology, Investigation, Formal analysis, Data curation, Writing – Original Draft, Writing – review & editing. ABI: Conceptualization, Methodo-logy. IRRM: Writing – review & editing. JMCS: Formal analysis. PMPF: Formal analysis, Writing – review & editing. FCCS: Conceptualization, Project administration, Resources, Supervision.
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/10937404.2023.2246876
Abbreviations
| 17AAG | = | 17-(allylamino)-17-demethoxygeldanamycin |
| 2DG | = | 2-deoxyglucose |
| ATN-224 | = | Tetrathiomolybdate |
| ATO | = | Arsenic trioxide |
| BCNU | = | 1,3-bis(2-chloroethyl)-1-nitrosourea/Carmustine |
| BSO | = | Buthionine sulfoximine |
| CDDP | = | Cisplatin |
| CDX | = | Cell-line-derived xenographic models |
| CFA | = | Cyclophosphamide |
| COX-2 | = | Cyclooxygenase-2 |
| DOX | = | Doxorubicin |
| GPX | = | Glutathione peroxidase |
| GSH | = | Glutathione |
| GSS | = | Gutathione synthetase |
| L-PAM | = | Melphalan |
| MRP1 | = | Multidrug resistance protein 1 |
| NA-CAP | = | N-acetyl-4-S-cysteaminylphenol |
| ROS | = | Reactive oxygen species |
| SN-38 | = | Active metabolite of irinotecan |
| TETRAC | = | Tetraiodothyroacetic acid |
| VEGF | = | Vascular endothelial growth factor |
| µGCS | = | µ-glutamil-cisteína sintetase |
| γGCS | = | γ-glutamylcysteine |
| MSO | = | methionine sulfoximine |
| SYRCLE | = | Systematic Review Center for Laboratory Animal Experimentation |
| TNF-α | = | Alpha tumor necrosis factor |
| ATCC | = | American Type Culture Collection |
| m@Au-d/B NCs | = | Cell membrane-camouflaged gold nanocages |
| PDT | = | Photodynamic therapy |
| SMD | = | Standardized mean difference |
| SD | = | Standard deviations |
| SEM | = | Standard error of the mean |