Cancer chemopreventive activity and metabolism of isoliquiritigenin, a compound found in licorice.
Isoliquiritigenin (2',4',4-trihydroxychalcone; ILG), a chalcone found in licorice root and many other plants, has shown potential chemopreventive activity through induction of phase II enzymes such as quinone reductase-1 in murine hepatoma cells. In this study, the in vivo metabolism of ILG was investigated in rats. In addition, ILG glucuronides and ILG-glutathione adducts were observed in human hepatocytes and in livers from rats treated with ILG. ILG glucuronides were detected in both plasma and rat liver tissues. In addition, in a full-term cancer chemoprevention study conducted with 7,12-dimethylbenz(a)anthracene-treated female Sprague-Dawley rats, dietary administration of ILG slightly increased tumor latency but had a negative effect on the incidence of mammary tumors starting at approximately 65 days after 7,12-dimethylbenz(a)anthracene administration. Further, no significant induction of phase II enzymes was found in mammary glands, which is consistent with the low level of ILG observed in these tissues. However, ILG significantly induced quinone reductase-1 activity in the colon, and glutathione as well as glutathione S-transferase in the liver. Analysis of mRNA expression in tissues of rats treated with ILG supported these findings. These results suggest that ILG should be tested for chemopreventive efficacy in nonmammary models of cancer.
Cuendet
Muriel
M
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana, USA.
Guo
Jian
J
Luo
Yan
Y
Chen
Shaonong
S
Oteham
Carol P
CP
Moon
Richard C
RC
van Breemen
Richard B
RB
Marler
Laura E
LE
Pezzuto
John M
JM
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D047188:Chalcones / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D018890:Chemoprevention / Q000379:methods; D002853:Chromatography, Liquid; D003106:Colon / Q000187:drug effects / Q000201:enzymology; D005260:Female; D005978:Glutathione / Q000187:drug effects; D005982:Glutathione Transferase / Q000187:drug effects; D006035:Glycyrrhiza / Q000737:chemistry; D006801:Humans; D008099:Liver / Q000187:drug effects; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000517:prevention & control*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000187:drug effects; D008517:Phytotherapy / Q000379:methods*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053719:Tandem Mass Spectrometry
D000970:Antineoplastic Agents; D047188:Chalcones; D012333:RNA, Messenger; C040920:isoliquiritigenin; D016660:NAD(P)H Dehydrogenase (Quinone); D005982:Glutathione Transferase; D005978:Glutathione