Zebularine is a DNA methylation inhibitor which forms a covalent complex with DNA methyltransferases, it also inhibits cytidinedeaminase with Ki of 2 μM.
The DNA methyltransferase (DNMT) family are enzymes that can mediate the DNA methylation. Inhibiting the DNMTs have shown particular promise in reducing the formation of tumors[6]. Zebularine is a second-generation inhibitor of DNMT with IC50 value of 95 nM on DNMT1[7]. The TFK-1 and HuCCT1 cells were treated with zebularine from 100 - 1000 µM for 72 hours. The cell viability was significantly reduced in a dose dependent manner measured by WST assay. The protein expression level of DNMT1, DNMT3a, DNMT3b examined by western blotting assay was significantly inhibited for both cell lines at concentration of 400 µM and above[8]. BALB/c nude mice with tumor were treated with 10, 50 and 100 mg/kg zebularine via oral gavage in a solution of 0.45% saline every four days for 20 days. The tumor growth was reduced in a dose dependent manner and the cell death in the tumor mass via apoptosis was induced by the treatement of zebularine as measured by the TUNEL assay[9].
作用机制
Zebularine could form tight covalent complexes between the DNMT proteins and zebularine-substitute DNA[10].
Zebularine 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
human HCT15 cells
100 μM
Function assay
8 days
Induction of p16 gene expression in human HCT15 cells at 100 uM after 8 days by real time PCR in presence of 100 mM thymidine
19006382
human T24 cells
100 μM
Function assay
8 days
Induction of p16 gene expression in human T24 cells at 100 uM after 8 days by real time PCR in presence of 100 mM thymidine
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