Berberine induces apoptosis in human multiple myeloma cell line U266 through hypomethylation of p53 promoter.
Berberine has multiple pharmacological activities, such as anti-oxidative, anti-inflammation and anticancer activity. It reduces the proliferation and induces apoptosis in the multiple myeloma cell line, U266. Here we explored the detailed mechanism by analysing the gene expression profiles in U266 treated with or without berberine. DNMT1 andDNMT3B, encoding for a highly conserved member of the DNA methyltransferases, decreased significantly. By dissection of biochemical network database (BNDB) with Kyoto Encyclopaedia of Genes and Genomes (KEGG) annotation, the p53 signalling pathway related genes were altered. By using epigenetic chromatin modification enzymes PCR Array, gene expression microarray, RT-PCR and Bisulphite sequencing, the results show that berberine can repress the expression of DNMT1 and DNMT3B, which triggers hypomethylation of TP53 by changing the DNA methylation level and the alteration of p53 dependent signal pathway in human multiple melanoma cell U266.
Yanwei
Y
Qing
Haiyan
H
Hu
Yuan
Y
Liu
Tao
T
Feng
Wei
W
Meng
Ling
L
Jiang
Yongning
Y
Sun
Yang
Y
Yao
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001599:Berberine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D009101:Multiple Myeloma / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D016159:Tumor Suppressor Protein p53; D001599:Berberine