Berberine acts as a putative epigenetic modulator by affecting the histone code.
Berberine, an isoquinoline plant alkaloid, exhibits a wide range of biochemical and pharmacological effects. However, the precise mechanism of these bioactivities remains poorly understood. In this study, we found significant similarity between berberine and two epigenetic modulators (CG-1521 and TSA). Reverse-docking using berberine as a ligand identified lysine-N-methyltransferase as a putative target of berberine. These findings suggested the potential role of berberine in epigenetic modulation. The results of PCR array analysis of epigenetic chromatin modification enzymes supported our hypothesis. Furthermore, the analysis showed that enzymes involved in histone acetylation and methylation were predominantly affected by treatment with berberine. Up-regulation of histone acetyltransferase CREBBP and EP300, histone deacetylase SIRT3, histone demethylase KDM6A as well as histone methyltransferase SETD7, and down-regulation of histone acetyltransferase HDAC8, histone methyltransferase WHSC1I, WHSC1II and SMYD3, in addition to 38 genes from histone clusters 1-3 were observed in berberine-treated cells using real-time PCR. In parallel, western blotting analyses revealed that the expression of H3K4me3, H3K27me3 and H3K36me3 proteins decreased with berberine treatment. These results were further confirmed in acute myelocytic leukemia (AML) cell lines HL-60/ADR and KG1-α. Taken together, this study suggests that berberine might modulate the expression of epigenetic regulators important for many downstream pathways, resulting in the variation of its bioactivities.
Department of Hematology, Nanfang Hospital of Southern Medical University, Guangzhou, China.
Zhixiang
Z
Wang
Department of Hematology, The Third Hospital of Nanchang City, Nanchang, China.
Yuan
Y
Liu
Jiangxi Science & Technology Research Center for Safety, Jiangxi, China.
Yong
Y
Xue
Department of Oncology, 6th People's Hospital of Shanghai, Shanghai, China.
Haiyan
H
Hu
Department of Hematology, Nanfang Hospital of Southern Medical University, Guangzhou, China.
Jieyu
J
Ye
Department of Hematology, Nanfang Hospital of Southern Medical University, Guangzhou, China.
Xiaodong
X
Li
Department of Blood Transfusion, Zhujiang Hospital of Southern Medical University, Guangzhou, China.
Zhigang
Z
Lu
Department of Hematology, Nanfang Hospital of Southern Medical University, Guangzhou, China.
Fanyi
F
Meng
Department of Neuroscience, Southern Medical University, Guangzhou, China. Electronic address: itshuang@gmail.com.
Shuang
S
Liang
D000107:Acetylation / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects; D001599:Berberine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation / Q000187:drug effects; D042421:Histone Code / Q000187:drug effects*; D006801:Humans; D008745:Methylation / Q000187:drug effects; D062105:Molecular Docking Simulation
D001599:Berberine
Berberine; Epigenetic; Hematological malignancy; Histone; Methylation