Ursodeoxycholic acid prompts glycolytic dominance, reductive stress and epithelial-to-mesenchymal transition in ovarian cancer cells through NRF2 activation

Numerous secreted bacterial metabolites were identified with bioactivity in various neoplasias, including ovarian cancer. One such metabolite is ursodeoxycholic acid (UDCA), a secondary bile acid that has widespread beneficial effects in neoplasias. Hereby, we assessed the bioactivity of UDCA in cell models of ovarian cancer, by applying UDCA in concentrations corresponding to the serum reference concentrations of UDCA (300 nM). UDCA induced epithelial-to-mesenchymal transition (EMT), increased the flux of glycolysis and reduced the naturally occurring oxidative stress in ovarian cancer cells. These changes were dependent on the activation of NRF2. The tumoral overexpression of UDCA-induced genes in humans correlated with worse survival. These results point out that bacterial metabolites may have opposite effects in different neoplasias and raise the possibility that UDCA-containing remedies on the long run may support cancer progression in ovarian cancer patients.