Antagonistic Effect of Low-dose Liquiritigenin on Gemcitabine-induced Capillary Leak Syndrome
- Wei Wu, Rui - Jie Luo, Zi - Qi Lin, Ping Xue
The nucleoside kinases phosphorylate nucleosides to corresponding nucleoside 5'-monophosphates. Their activities are essential for activation of chemotherapeutically important nucleoside analogues. Since, among them, deoxycytidine kinase has high activity in a wide variety of tumor tissues, a relatively low substrate specificity, and is not cell-cycle regulated, 2'-substituted-2'-deoxycytidine analogues should be suitable for antitumor antimetabolites. Gemcitabine, DMDC, and CNDAC have been developed for such analogues. These nucleosides showed potent antitumor activity against various solid tumors. They inhibited mainly DNA synthesis of tumor cells and, to some extent, inhibited RNA synthesis. To inhibit RNA synthesis of tumor cells would be important to kill solid tumor cells, which are heterogenous. ECyd was designed as an inhibitor of both DNA and RNA syntheses and showed potent antitumor activity against a variety of human tumor cells in xenografts.