Abstract
Metastasis is the process by which cancer cells are disseminated from their primary site to distant locations, causing complications in anti-cancer treatments and a high rate of mortality. Therefore, the discovery of novel drug candidates that can inhibit metastasis progression is crucial for improving anti-cancer therapeutic outcomes. Tauro ursodeoxycholic acid (TUDCA) is a bile acid with known cytoprotective and anti-apoptotic properties. In this study, we investigated the anti-metastatic activity of TUDCA in 12-O-tetradecanoylphorbol-13-acetate (PMA) stimulated human fibrosarcoma HT-1080 cells. TUDCA treatment decreased cell viability in a dose-dependent manner in HT-1080 cells. TUDCA displayed the antimetastatic effect by significantly inhibiting the cell invasion and migration in HT-1080 cells at 5, 10, and 20 µM (p < 0.05). Gelatin zymography revealed that TUDCA inhibited the MMP2 and MMP9 activities in HT-1080 cells in a concentration-dependent manner. Western blot analysis showed that TUDCA treatment inhibited the phosphorylation of MAPK pathway-related ERK, JNK, and p38, along with suppression of nuclear translocation of p-p65 and c-FOS, confirming that TUDCA could modulate MAPK and NF-κB pathways for anti-metastatic activity. Furthermore, gene reporter assay confirmed that TUDCA inhibited the transcriptional activity of NF-κB and AP1. These results suggest that TUDCA could exert a potent anti-metastatic activity in PMA-stimulated HT-1080 cells through modulation of MMPs, MAPKs signaling pathway, and NF-κB and AP1 transcription factors.