Lipoyl-Based Antagonists of Transient Receptor Potential Cation A (TRPA1) Downregulate Osteosarcoma Cell Migration and Expression of Pro-Inflammatory Cytokines.

Autor:	Francesconi O; Department of Chemistry, DICUS, University of Florence, via della Lastruccia, 3-13, Sesto Fiorentino, 50019Florence, Italy., Corzana F; Departamento de Química, Centro de Investigación en Síntesis Química, Universidad de La Rioja, 26006Logroño, Spain., Kontogianni GI; Department of Materials Science and Technology, University of Crete, 70013Heraklion, Greece., Pesciullesi G; Department of Chemistry, DICUS, University of Florence, via della Lastruccia, 3-13, Sesto Fiorentino, 50019Florence, Italy., Gualdani R; Department of Chemistry, DICUS, University of Florence, via della Lastruccia, 3-13, Sesto Fiorentino, 50019Florence, Italy., Supuran CT; NEUROFARBA Department, Sezione di Scienze Farmaceutiche, University of Florence, Via Ugo Schiff 6, Sesto Fiorentino, 50019Florence, Italy., Angeli A; NEUROFARBA Department, Sezione di Scienze Farmaceutiche, University of Florence, Via Ugo Schiff 6, Sesto Fiorentino, 50019Florence, Italy., Kavasi RM; Foundation for Research and Technology Hellas (FORTH), Institute of Electronic Structure and Laser (IESL), 70013Heraklion, Greece., Chatzinikolaidou M; Department of Materials Science and Technology, University of Crete, 70013Heraklion, Greece.; Foundation for Research and Technology Hellas (FORTH), Institute of Electronic Structure and Laser (IESL), 70013Heraklion, Greece., Nativi C; Department of Chemistry, DICUS, University of Florence, via della Lastruccia, 3-13, Sesto Fiorentino, 50019Florence, Italy.
Jazyk:	angličtina
Zdroj:	ACS pharmacology & translational science [ACS Pharmacol Transl Sci] 2022 Sep 13; Vol. 5 (11), pp. 1119-1127. Date of Electronic Publication: 2022 Sep 13 (Print Publication: 2022).
DOI:	10.1021/acsptsci.2c00114
Abstrakt:	Osteosarcoma is a heterogeneous tumor intimately linked to its microenvironment, which promotes its growth and spread. It is generally accompanied by cancer-induced bone pain (CIBP), whose main component is neuropathic pain. The TRPA1 ion channel plays a key role in metastasis and is increasingly expressed in bone cancer. Here, a novel TRPA1 inhibitor is described and tested together with two other known TRPA1 antagonists. The novel lipoyl derivative has been successfully assessed for its ability to reduce human osteosarcoma MG-63 cell viability, motility, and gene expression of the CIBP pro-inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α). A putative three-dimensional (3D) model of the inhibitor covalently bound to TRPA1 is also proposed. The in vitro data suggest that the novel inhibitor described here may be highly interesting and stimulating for new strategies to treat osteosarcomas. Competing Interests: The authors declare no competing financial interest. (© 2022 American Chemical Society.)
Databáze:	MEDLINE
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