Curcumin is a potent DNA hypomethylation agent.
Molecular docking of the interaction of curcumin and DNMT1 suggested that curcumin covalently blocks the catalytic thiolate of C1226 of DNMT1 to exert its inhibitory effect. This was validated by showing that curcumin inhibits the activity of M. SssI with an IC(50) of 30 nM, but no inhibitory activity of hexahydrocurcumin up to 100 microM. In addition, curcumin can induce global DNA hypomethylation in a leukemia cell line.
Liu
Zhongfa
Z
Division of Pharmaceutics, College of Pharmacy, The Ohio State University, 500 W. 12th St., Columbus, OH 43210, USA. liu.550@osu.edu
Xie
Zhiliang
Z
Jones
William
W
Pavlovicz
Ryan E
RE
Liu
Shujun
S
Yu
Jianhua
J
Li
Pui-kai
PK
Lin
Jiayuh
J
Fuchs
Jame R
JR
Marcucci
Guido
G
Li
Chenglong
C
Chan
Kenneth K
KK
D002384:Catalysis; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D003474:Curcumin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D003596:Cytosine / Q000737:chemistry; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000737:chemistry; D019175:DNA Methylation; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D007938:Leukemia / Q000188:drug therapy; D008956:Models, Chemical; D008968:Molecular Conformation
C096277:tetrahydrocurcumin; D003596:Cytosine; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; D003474:Curcumin