A Triazaspirane Derivative Inhibits Migration and Invasion in PC3 Prostate Cancer Cells

Molecules. 2023 Jun 2;28(11):4524. doi: 10.3390/molecules28114524.

Abstract

Cancer is a serious health problem due to the complexity of establishing an effective treatment. The purpose of this work was to evaluate the activity of a triazaspirane as a migration and invasion inhibitor in PC3 prostatic tumor cells through a possible negative regulation of the FAK/Src signal transduction pathway and decreased secretion of metalloproteinases 2 and 9. Molecular docking analysis was performed using Moe 2008.10 software. Migration (wound-healing assay) and invasion (Boyden chamber assay) assays were performed. In addition, the Western blot technique was used to quantify protein expression, and the zymography technique was used to observe the secretion of metalloproteinases. Molecular docking showed interactions in regions of interest of the FAK and Src proteins. Moreover, the biological activity assays demonstrated an inhibitory effect on cell migration and invasion, an important suppression of metalloproteinase secretion, and a decrease in the expression of p-FAK and p-Src proteins in treated PC3 cells. Triazaspirane-type molecules have important inhibitory effects on the mechanisms associated with metastasis in PC3 tumor cells.

Keywords: FAK; PC3; Src; prostate cancer; triazaspirane.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Humans
  • Male
  • Metalloproteases / pharmacology
  • Molecular Docking Simulation
  • Neoplasm Invasiveness
  • Neoplastic Processes
  • PC-3 Cells
  • Prostatic Neoplasms* / pathology

Substances

  • Metalloproteases