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Stilbene compound trans-3,4,5,4′-tetramethoxystilbene, a potential anticancer drug, regulates constitutive androstane receptor (Car) target genes, but does not possess proliferative activity in mouse liver.

Toxicol. Lett.. 2019; 
DusekJan,SkodaJosef,HolasOndrej,HorvatovaAlzbeta,SmutnyTomas,LinhartovaLenka,HirsovaPetra,KuceraOtto,MicudaStanislav,BraeuningAlbert,Pavek
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Bacterial Expression System The mouse PXR (Pxr) expression construct was provided by Genscript (Piscataway, NJ, USA) (Clone ID: OMu17834D, NM_010936. Get A Quote

摘要

The constitutive androstane receptor(CAR) activation is connected with mitogenic effects leading to liver hyperplasia and tumorigenesis in rodents. CAR activators, including phenobarbital, are considered rodent non-genotoxic carcinogens. Recently, trans-3,4,5,4′-tetramethoxystilbene(TMS), a potential anticancer drug (DMU-212), have been shown to alleviate N-nitrosodiethylamine/phenobarbital-induced liver carcinogenesis. We studied whether TMS inhibits mouse Car to protect from the PB-induced tumorigenesis. Unexpectedly, we identified TMS as a murine CAR agonist in reporter gene experiments, in mouse hepatocytes, and in C57BL/6 mice in vivo. TMS up-regulated Car target genes Cyp2b10, Cy... More

关键词

Constitutive androstane receptor,Gene regulation,Ligand,Metabolism,Mouse,Tumorigen