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Evaluation of 1,3,8-Triazaspiro[4.5]decane-2,4-Dione and Its Relationship with the FAK/Src Pathway in Prostate Cancer Cells
By Vasconcelos-Ulloa JdJ, García-González V, Rivero- Espejel I and 5 others.
Abstract
Cancer is known as a microevolutionary disease associated with genetic and epigenetic modifications, which is considered a global problem for which there is no fully effective treatment. Prostate cancer (PCa) is the second most commonly diagnosed cancer in men, with 1,414,259 new global cases (14.1%) in 2020. The aim of the present study was to evaluate the activity of a molecule of the triazaspirane family in PC3 PCa cells, through possible negative regulation of the FAK/Src signal transduction pathway. A molecular docking assay was performed using the compound 1,3,8-triazaspiro[4.5]decane-2,4-dione (TSDD) against FAK and Src. Migration and invasion assays were performed on PC3 PCa cells. In addition, the protein expression levels of phosphorylated p-FAK, p-Src, E-cadherin and N-cadherin were determined, and MMP-9 secretion was analysed. Molec-ular docking assays showed interactions in the regions of interest of FAK and Src proteins, and biological activity assays demonstrated an inhibitory effect on cell migration and in-vasion. In addition, a significant suppression of MMP-9 secretion was detected in treated PC3 cells, as well as a decrease in the expression of p-FAK and p-Src proteins. In conclu-sion, the TSDD molecule demonstrated inhibitory effects related to cell migration and in-vasion in an in vitro model of PCa.



