Sipos Adrienn, Kerekes Éva, Szeőcs Dóra, Szarvas Fanni, Schwarcz Szandra, Tóth Emese, Ujlaki Gyula, Mikó Edit, Bai Peter
Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
HUN-REN Cell Biology and Signaling Research Group, Debrecen, Hungary.
Cell Death Discov. 2025 Apr 3;11(1):134. doi: 10.1038/s41420-025-02398-9.
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.
在包括卵巢癌在内的各种肿瘤中，已鉴定出许多具有生物活性的分泌型细菌代谢物。其中一种代谢物是熊去氧胆酸（UDCA），一种在肿瘤中具有广泛有益作用的次级胆汁酸。在此，我们通过应用与UDCA血清参考浓度（300 nM）相对应的浓度的UDCA，评估了UDCA在卵巢癌细胞模型中的生物活性。UDCA诱导上皮-间质转化（EMT），增加糖酵解通量，并降低卵巢癌细胞中自然发生的氧化应激。这些变化依赖于NRF2的激活。人类中UDCA诱导基因的肿瘤过表达与较差的生存率相关。这些结果指出，细菌代谢物在不同肿瘤中可能具有相反的作用，并提出长期使用含UDCA的药物可能会促进卵巢癌患者癌症进展的可能性。
