Antiproliferation of berberine is mediated by epigenetic modification of constitutive androstane receptor (CAR) metabolic pathway in hepatoma cells.
Constitutive androstane receptor (CAR) regulates hepatic xenobiotic and energy metabolism, as well as promotes cell growth and hepatocarcinogenesis. Berberine is an ancient multipotent alkaloid drug which derived from Coptis chinensis plants. Here we report that berberine is able to be cellular uptake and accessible to chromatin in human hepatoma HepG2 cells. Berberine induces more apoptosis, cell cycle arrest, but less ROS production in CAR overexpressed mCAR-HepG2 cells. Moreover, berberine inhibits expressions of CAR and its target genes CYP2B6 and CYP3A4. Furthermore, berberine enhances DNA methylation level in whole genome but reduces that in promoter regions CpG sites of CYP2B6 and CYP3A4 genes under the presence of CAR condition. These results indicated that the antiproliferation of berberine might be mediated by the unique epigenetic modifying mechanism of CAR metabolic pathway, suggesting that berberine is a promising candidate in anticancer adjuvant chemotherapy, due to its distinct pharmacological properties in clinic.
Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
Lei
L
Zhang
Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
Xiao-Jie
XJ
Miao
Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
Xin
X
Wang
Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
Hai-Hui
HH
Pan
Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
Pu
P
Li
Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
Hong
H
Ren
Medical and Healthy Analytical Center, Peking University, Beijing, 100191, China.
Yong-Rui
YR
Jia
Department of Drug Metabolism &Pharmacokinetics, Biogen, Cambridge, Massachusetts, USA.
Chuang
C
Lu
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, USA.
Hong-Bing
HB
Wang
Medical and Healthy Analytical Center, Peking University, Beijing, 100191, China.
Lan
L
Yuan
Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
Guo-Liang
GL
Zhang
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001599:Berberine / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D000090702:Constitutive Androstane Receptor; D065702:Cytochrome P-450 CYP2B6 / Q000096:biosynthesis / Q000235:genetics; D051544:Cytochrome P-450 CYP3A / Q000096:biosynthesis / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects* / Q000235:genetics; D044127:Epigenesis, Genetic; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D011401:Promoter Regions, Genetic / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D000090702:Constitutive Androstane Receptor; D017382:Reactive Oxygen Species; D018160:Receptors, Cytoplasmic and Nuclear; D001599:Berberine; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human