Purpose: Citric acid (CA) is a tricarboxylic acid with antioxidant and antimicrobial properties. Based on previous studies, the small compound with its three carboxylic groups can be considered a protein tyrosine phosphatase inhibitor. YopH, a protein tyrosine phosphatase, is an essential virulence factor in Yersinia bacteria. Materials and Methods: We performed enzymatic activity assays of YopH phosphatase after treatment with citric acid in comparison with the inhibitory compound trimesic acid, which has a similar structure. We also measured the cytotoxicity of these compounds in Jurkat T E6.1 and macrophage J774.2 cell lines. We performed molecular docking analysis of the binding of citric acid molecules to YopH phosphatase. Results: Citric acid and trimesic acid reversibly reduced the activity of YopH enzyme and decreased the viability of Jurkat and macrophage cell lines. Importantly, these two compounds showed greater inhibitory properties against bacterial YopH activity than against human CD45 phosphatase activity. Molecular docking simulations confirmed that citric acid could bind to YopH phosphatase. Conclusion: Citric acid, a known antioxidant, can be considered an inhibitor of bacterial phosphatases.
Antioxidants , Protein Tyrosine Phosphatases , Tricarboxylic Acids , Humans , Molecular Docking Simulation , Protein Tyrosine Phosphatases/chemistry , Protein Tyrosine Phosphatases/metabolism , Tyrosine
BACKGROUND/AIM: PTP1B tyrosine phosphatase is involved in the development of many types of cancers, such as breast cancer or lung cancer. Therefore, PTP1B is a promising target for anticancer therapy. The purpose of this review was to present the studies on selected PTP1B inhibitors as a possible treatment and describe the latest trends of current research in this field. MATERIALS AND METHODS: This literature review was performed using the PubMed database and the analysis of previous research studies of our Department. RESULTS: Recent studies have shown that PTP1B, due to its implication in oncogenic transformation, represents a promising drug target. CONCLUSION: The selected compounds that are effective PTP1B inhibitors can be considered a promising anticancer treatment, both as monotherapy and in combination with other anticancer drugs.
Antineoplastic Agents/therapeutic use , Neoplasms/drug therapy , Protein Tyrosine Phosphatase, Non-Receptor Type 1/antagonists & inhibitors , Antineoplastic Agents/pharmacology , Humans , Neoplasms/metabolism , Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism , src-Family Kinases/metabolism
