Quercetin, a bioflavonoid, inhibits the increase of human multidrug resistance gene (MDR1) expression caused by arsenite.
Expression of the MDR1 gene, which encodes P-glycoprotein, is increased under some stress conditions. We have reported that quercetin, a bioflavonoid, inhibits the expression of heat-shock proteins. We have identified the effects of quercetin on the MDR1 gene expression in the human hepatocarcinoma cells line, HepG2. The increase of P-glycoprotein synthesis and MDR1 mRNA accumulation caused by exposure to arsenite were inhibited by quercetin. The CAT assay suggested that quercetin suppressed the transcriptional activation of the MDR1 gene after exposure to arsenite. Although many drugs that prevent the P-glycoprotein function have been reported, this is the first report to describe the inhibition of MDR1 expression by a reagent.
Kioka
N
N
Department of Agricultural Chemistry, Kyoto University, Japan.
Hosokawa
N
N
Komano
T
T
Hirayoshi
K
K
Nagata
K
K
Ueda
K
K
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001151:Arsenic / Q000494:pharmacology*; D018053:Arsenites; D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004336:Drug Antagonism; D004351:Drug Resistance; D015870:Gene Expression / Q000187:drug effects*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D010957:Plasmids; D011794:Quercetin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018053:Arsenites; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011794:Quercetin; D015500:Chloramphenicol O-Acetyltransferase; C015001:arsenite; D001151:Arsenic