Frontiers in Molecular Biosciences | |
Targeting phosphoglycerate kinases by tatridin A, a natural sesquiterpenoid endowed with anti-cancer activity, using a proteomic platform | |
Molecular Biosciences | |
Matteo Mozzicafreddo1  Federica Pollastro2  Maria Chiara Monti3  Alessandra Tosco3  Antonia Voli4  Giusy Ferraro4  | |
[1] Department of Clinical and Molecular Sciences, Università Politecnica Delle Marche, Ancona, Italy;Department of Pharmaceutical Sciences, Università Del Piemonte Orientale, Novara, Italy;PlantaChem Srls, Novara, Italy;Department of Pharmacy, Università di Salerno, Fisciano, Italy;Department of Pharmacy, Università di Salerno, Fisciano, Italy;PhD Program in Drug Discovery and Development, Department of Pharmacy, Università di Salerno, Fisciano, Italy; | |
关键词: sesquiterpenes; functional proteomics; PGK1; CXCR4; gastric cancer; cancer dissemination; | |
DOI : 10.3389/fmolb.2023.1212541 | |
received in 2023-04-26, accepted in 2023-07-10, 发布年份 2023 | |
来源: Frontiers | |
【 摘 要 】
Tatridin A (TatA) is a germacrane sesquiterpenoid containing one E-double bond and one Z-double bond in its 10-membered ring, which is fused to a 3-methylene-dihydrofuran-2-one moiety. Tatridin A bioactivity has been poorly investigated despite its interesting chemical structure. Here, a functional proteomic platform was adapted to disclose its most reliable targets in leukemia monocytic cells, and phosphoglycerate kinases were recognized as the most affine enzymes. Through a combination of limited proteolysis and molecular docking, it has been discovered that tatridin A interacts with the active domains of phosphoglycerate kinase 1, altering its hinge region, and it can be accountable for tatridin A inhibition potency on enzyme activity. A more detailed tatridin A biological profile showed that it is also fully active against gastric cancer cells, downregulating the mRNA levels of chemokine receptor 4 and β-catenin and inhibiting the invasiveness of living KATO III cells as a direct consequence of phosphoglycerate kinase 1 antagonism.
【 授权许可】
Unknown
Copyright © 2023 Ferraro, Voli, Mozzicafreddo, Pollastro, Tosco and Monti.
【 预 览 】
Files | Size | Format | View |
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RO202310127651886ZK.pdf | 1756KB | download |