Tetrahydrouridine Inhibits Cell Proliferation through Cell Cycle Regulation Regardless of Cytidine Deaminase Expression Levels
Figure 3
Metabolic pathway of gemcitabine.
Gemcitabine (2′,2′-difluorodeoxycytidine, dFdC) is taken in DNA through the active diphosphate (dFdCDP) and triphosphate (dFdCTP) by deoxycytidine kinase (dCK). dFdCTP can inhibit ribonucleotide reductase (RR). On the contrary, Cytidine deaminase (CDA) inactivates dFdC to 2′,2′-difluorodeoxyuridine (dFdU) by deamination. Tetrahydrouridine (THU) prevents dFdC from being inactivated by binding CDA directly. THU also leads to the potential for cell growth inhibition.