Fli-1 Activation through Targeted Promoter Activity Regulation Using a Novel 3', 5'-diprenylated Chalcone Inhibits Growth and Metastasis of Prostate Cancer Cells.

The friend leukemia integration 1 (Fli-1) gene is involved in the expression control of key genes in multiple pathogenic/physiological processes, including cell growth, differentiation, and apoptosis; this implies that Fli-1 is a strong candidate for drug development. In our previous study, a 3',5'-diprenylated chalcone, (E)-1-(2-hydroxy-4-methoxy-3,5-diprenyl) phenyl-3-(3-pyridinyl)-propene-1-one (), was identified as a novel anti-prostate cancer (PCa) agent. Here, we investigated the molecular mechanisms underlying the anti-cancer effects of on the growth, metastasis, and invasion of PC3 cells in vitro. Our results show that exhibited a strong inhibitory effect on proliferation and metastasis of PC3 cells via several cellular and flow cytometric analyses. Further mechanism studies revealed that likely serves as an Fli-1 agonist for regulating the expression of Fli-1 target genes including phosphatidylinositol 3-kinase (), murine double minute2 (), B-cell lymphoma-2 (), Src homology-2 domain-containing inositol 5-phosphatase 1 (), and globin transcription factor-1 () as well as the phosphorylation of extracellular-regulated protein kinases 1 (). Further, we confirmed that C10 can regulate the expressions of vascular endothelial growth factor 1 (), transforming growth factor-β2 (), intercellular cell adhesion molecule-1 (), p53, and matrix metalloproteinase 1 () genes associated with tumor apoptosis, migration, and invasion. Thus, exhibits stronger anticancer activity with novel molecular targets and regulatory molecular mechanisms, indicating its great potency for development as a novel targeted anticancer drug.