Linked Life Data

16829687

Source:http://linkedlifedata.com/resource/pubmed/id/16829687

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2006-11-27
pubmed:abstractText
Typically chemopreventive agents either induce phase II detoxifying enzymes or inhibit the cytochrome P450 enzymes (CYPs) that are required for the metabolism of carcinogens. In this study, we isolated a coumarin compound, isoimperatorin from Poncirus trifoliata Raf., and studied its protective effects against aflatoxin B1 (AFB1)-induced cytotoxicity in H4IIE cells. Isoimperatorin (>0.3 microM) significantly inhibited the cytotoxic effect of AFB1. CDNB [1-chloro-2,4-dinitrobenzene; glutathine S-transferase (GST) subtype-non-specific] and NBD (7-chloro-4-nitrobenzo-2-oxa-1,3-diazole; GSTalpha type-specific) assays revealed that isoimperatorin (0.3-3 microM) increased GST activity in a concentration-dependent manner. Western blot analyses using subtype-specific antibodies confirmed that GSTalpha protein, but not GSTmu or GSTpi, was induced in cells treated with isoimperatorin. Reporter gene analysis using an antioxidant response element (ARE) containing construct and subcellular fractionation assays revealed that GSTalpha induction by isoimperatorin is associated with Nrf2/ARE activation. Moreover, ethoxyresorufin-O-deethylase assays showed that isoimperatorin (2 microM) completely inhibited 3-methylchoranthrene-inducible CYP1A activity. These results indicate that isoimperatorin from Poncirus trifoliata Raf. possesses a potent hepatoprotective effect against AFB1, presumably through the induction of GSTalpha and the direct inhibition of CYP1A, and suggest that isoimperatorin should be considered a potential chemopreventive.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2483-90
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Potent protective effect of isoimperatorin against aflatoxin B1-inducible cytotoxicity in H4IIE cells: bifunctional effects on glutathione S-transferase and CYP1A.
pubmed:affiliation
College of Pharmacy, Chosun University Seosuk-dong, Dong-gu, Gwangju 501-759, South Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't