Learn More
NQO1 is an emerging and promising therapeutic target in cancer therapy. This study was to determine whether the anti-tumor effect of tanshinone IIA (TSA) is NQO1 dependent and to elucidate the underlying apoptotic cell death pathways. NQO1(+) A549 cells and isogenically matched NQO1 transfected and negative H596 cells were used to test the properties and(More)
Edaravone was launched in Japan in 2001 and was the first neuroprotectant developed for the treatment of acute cerebral infarction. Edaravone is mainly eliminated as glucuronide conjugate in human urine (approximately 70%), but the mechanism involved in the elimination pathway remains unidentified. We investigated the glucuronidation of edaravone in human(More)
BACKGROUND AND PURPOSE NAD(P)H: quinone oxidoreductase 1 (NQO1) mediated quinone reduction and subsequent UDP-glucuronosyltransferases (UGTs) catalyzed glucuronidation is the dominant metabolic pathway of tanshinone IIA (TSA), a promising anti-cancer agent. UGTs are positively expressed in various tumor tissues and play an important role in the metabolic(More)
UNLABELLED β-Lapachone (β-Lap) is an NAD(P)H quinone oxidoreductase 1 (NQO1) target antitumor drug candidate in phase II clinical trials. The present study aimed to uncover the metabolic profile, enzyme kinetics, and enzyme isoforms for the metabolism of β-Lap in human liver and intestine in vitro. NQO1-mediated quinone reduction and subsequent(More)
Bile acids play a pivotal role in the pathological development of inflammatory bowel disease (IBD). However, the mechanism of bile acid dysregulation in IBD remains unanswered. Here we show that intestinal peroxisome proliferator-activated receptor a (PPARa)-UDP-glucuronosyltransferases (UGTs) signalling is an important determinant of bile acid homeostasis.(More)
NAD(P)H:quinone oxidoreductase 1 (NQO1, DT-diaphorase) is a prognostic biomarker and a potential therapeutic target for various tumors. Therefore, it is of significance to develop a robust method for the absolute quantification of NQO1. This study aimed to develop and validate a LC-MS/MS based method and to test the appropriateness of using non-isotopic(More)
Pregnane X receptor (PXR) activation exhibits anti-inflammatory effects via repressing nuclear factor-κB (NF-κB); however, its overactivation may disrupt homeostasis of various enzymes and transporters. Here we found that ginsenosides restore PXR/NF-κB signaling in inflamed conditions without disrupting PXR function in normal conditions. The effects and(More)
Farnesoid X receptor (FXR) plays a pivotal role in the regulation of various metabolic pathways as well as liver regeneration. However, the casual link between cell proliferative effects during liver regeneration and metabolic regulation of FXR was elusive. In this study, we found that FXR activation significantly promotes HepG2 cell proliferation(More)
UDP-glucuronosyltransferase (UGT) is an important class of phase II metabolizing enzymes, playing a pivotal role in detoxifying various substances and in the pathological procedures of some diseases. The present study aims to uncover the potential dysregulation pattern of UGTs in trinitrobenzene sulfonic acid (TNBS)-induced colitis. Colitis was induced by(More)
Bile acids play a pivotal role in the pathological development of inflammatory bowel disease (IBD). However, the mechanism of bile acid dysregulation in IBD remains unanswered. Here we show that intestinal peroxisome proliferator-activated receptor α (PPARα)-UDP-glucuronosyltransferases (UGTs) signalling is an important determinant of bile acid homeostasis.(More)