Ursodeoxycholic acid suppresses epithelial-mesenchymal transition and cancer stem cell formation by reducing the levels of peroxiredoxin II and reactive oxygen species in pancreatic cancer cells.

ABSTRACT

Reactive oxygen species (ROS) play a key role in cancer development and progression. Ursodeoxycholic acid (UDCA) may possess antioxidant, anti-inflammatory and chemoprophylatic effects. Therefore, we aimed to investigate the effects and mechanisms of UDCA treatment on pancreatic cancer cells. The pancreatic cancer cell lines HPAC and Capan-1 were treated with 0.2 mM UDCA. To examine alterations in the levels of intracellular ROS, the DCF-DA stain was used and both stemness and epithelial-mesenchymal transition (EMT)-related genes were quantified using qRT-PCR and western blot analysis. The pancreatic cancer sphere culture was performed following seven days of treatment with 0.2 mM UDCA, as an indicator of stemness. Following treatment with UDCA, the level of intracellular ROS was decreased in the pancreatic cancer cells. UDCA decreased both the phosphorylation of STAT3 and the expression of peroxiredoxin II (Prx2). Furthermore, the treatment resulted in the upregulation of E-cadherin and in the downregulation of N-cadherin. In addition, UDCA decreased the expression of sex determining region Y-box 2 (Sox2) and it diminished the number of pancreatic cancer spheres formed. In conclusion UDCA suppressed the levels of intracellular ROS and Prx2 and it decreased EMT and stem cell formation in pancreatic cancer cells. Therefore, UDCA may provide favorable therapeutic benefits, through its antioxidant effects, for patients with pancreatic cancer.