Research Topics
Species | Thomas WalleSummaryAffiliation: Medical University of South Carolina Country: USA Publications
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Publications
Induction of UDP-glucuronosyltransferase UGT1A1 by the flavonoid chrysin in the human hepatoma cell line hep G2T Walle
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston 29425, USA
Drug Metab Dispos 28:1077-82. 2000..In view of these findings, it will be important to extend these studies to other dietary flavonoids...- Flavonoid glucosides are hydrolyzed and thus activated in the oral cavity in humansThomas Walle
Department of Cell and Molecular Pharmacology, Medical University of South Carolina, Charleston, SC 29425, USA
J Nutr 135:48-52. 2005..The large interindividual variability in this hydrolytic activity may be a factor that should be taken into consideration in future studies... - The dietary polyphenol ellagic acid is a potent inhibitor of hOAT1Alexander C Whitley
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA
Drug Metab Dispos 33:1097-100. 2005..In conclusion, we have demonstrated that the OAT family members hOAT1, rOat1, and hOAT4 mediate transport of EA, with a very high affinity for hOAT1... 
Bioavailability of resveratrolThomas Walle
Department of Pharmacology, Medical University of South Carolina, Charleston, 29425, USA
Ann N Y Acad Sci 1215:9-15. 2011..Resveratrol analogs, such as methylated derivatives with improved bioavailability, may be important in future research...- Benzo[A]pyrene-induced oral carcinogenesis and chemoprevention: studies in bioengineered human tissueThomas Walle
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 173 Ashley Avenue, P O Box 250505, Charleston, SC 29425, USA
Drug Metab Dispos 34:346-50. 2006..Thus, this bioengineered oral tissue construct opens up improved ways of understanding and preventing/treating smoking-induced oral cancer... 
Cancer chemopreventive properties of orally bioavailable flavonoids--methylated versus unmethylated flavonesThomas Walle
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA
Biochem Pharmacol 73:1288-96. 2007..Thus, fully methylated flavones appear to have great potential as cancer chemopreventive/chemotherapeutic agents, in particular in oral cancer...- Improving metabolic stability of cancer chemoprotective polyphenolsThomas Walle
Medical University of South Carolina, Department of Cell and Molecular Pharmacology and Experimental Therapeutics, 173 Ashley Avenue, Charleston, SC 29425, USA
Expert Opin Drug Metab Toxicol 3:379-88. 2007..Thus, permethylated polyphenols may have a future as chemoprotective agents... - Methoxylated flavones, a superior cancer chemopreventive flavonoid subclass?Thomas Walle
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, P O Box 250505, 173 Ashley Avenue, Charleston, SC 29425, USA
Semin Cancer Biol 17:354-62. 2007..It is concluded that the methoxyflavones have properties that may make them particularly useful as cancer chemopreventive agents... - Novel methoxylated flavone inhibitors of cytochrome P450 1B1 in SCC-9 human oral cancer cellsThomas Walle
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA
J Pharm Pharmacol 59:857-62. 2007.... - Methylation of dietary flavones greatly improves their hepatic metabolic stability and intestinal absorptionThomas Walle
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, South Carolina 29425, USA
Mol Pharm 4:826-32. 2007..Thus, methylation appears to be a simple and effective way of increasing both metabolic resistance and transport of the flavonoids and, most important, some of their major biological activities... - Methylation of dietary flavones increases their metabolic stability and chemopreventive effectsThomas Walle
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA E Mail Tel 1 843 795 3492
Int J Mol Sci 10:5002-19. 2009..In conclusion, it appears that methylation of dietary flavones as well as of other food products may produce derivatives with much improved health effects... - High absorption but very low bioavailability of oral resveratrol in humansThomas Walle
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA
Drug Metab Dispos 32:1377-82. 2004.... - Absorption and metabolism of flavonoidsThomas Walle
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA
Free Radic Biol Med 36:829-37. 2004..The impact of membrane transporters as well as metabolic enzymes on the cellular availability of these phytochemicals is examined. A reevaluation of the concept of oral bioavailability applied to the dietary flavonoids is presented... - The beta-D-glucoside and sodium-dependent glucose transporter 1 (SGLT1)-inhibitor phloridzin is transported by both SGLT1 and multidrug resistance-associated proteins 1/2Thomas Walle
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 173 Ashley Avenue, P O Box 250505, Charleston, SC 29425, USA
Drug Metab Dispos 31:1288-91. 2003..01). These results demonstrate that phloridzin, in contrast to previous notions, is transported by SGLT1. In addition, they demonstrate that this and other flavonoid glycosides unexpectedly are efficiently effluxed by both MRP1 and MRP2... - Disposition and metabolism of the flavonoid chrysin in normal volunteersT Walle
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Division of Clinical Pharmacology, Medical University of South Carolina, Charleston, SC 29425, USA
Br J Clin Pharmacol 51:143-6. 2001..To describe the oral disposition of the dietary flavonoid chrysin in healthy volunteers... - Carbon dioxide is the major metabolite of quercetin in humansT Walle
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA
J Nutr 131:2648-52. 2001..As much as 23.0-81.1% of the quercetin dose was recovered as (14)CO(2) in the expired air from these volunteers, after both oral and iv doses. The disposition of quercetin in humans is thus highly complex, requiring further studies... - Evidence of covalent binding of the dietary flavonoid quercetin to DNA and protein in human intestinal and hepatic cellsThomas Walle
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 173 Ashley Avenue, PO Box 250505, Charleston, SC 29425, USA
Biochem Pharmacol 65:1603-10. 2003..We propose that this specific binding may mediate part of the antiproliferative and other cellular actions of quercetin... - Bioavailable flavonoids: cytochrome P450-mediated metabolism of methoxyflavonesU Kristina Walle
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 173 Ashley Avenue, P O Box 250505, Charleston, SC 29425, USA
Drug Metab Dispos 35:1985-9. 2007..In summary, the rate of oxidative metabolism of methoxylated flavones, mainly involving CYP1A1 and CYP1A2, varied widely, even between compounds with very similar structures... - Site-specific accumulation of the cancer preventive dietary polyphenol ellagic acid in epithelial cells of the aerodigestive tractAlexander C Whitley
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 173 Ashley Avenue, PO Box 250505, Charleston, SC 29425, USA
J Pharm Pharmacol 58:1201-9. 2006..Finally, Caco-2 cells were shown to express organic anion transporter 4 (OAT4) mRNA, as was the human large intestine. EA appears to be accumulated along the aerodigestive tract using OAT-like transporters, one of which might be OAT4... - Methylated flavonoids have greatly improved intestinal absorption and metabolic stabilityXia Wen
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 173 Ashley Ave, P.O. Box 250505, Charleston, SC 29425, USA
Drug Metab Dispos 34:1786-92. 2006..The higher hepatic metabolic stability and intestinal absorption of the methylated polyphenols make them more favorable than the unmethylated polyphenols to be developed as potential cancer chemopreventive agents... - Preferential induction of CYP1B1 by benzo[a]pyrene in human oral epithelial cells: impact on DNA adduct formation and prevention by polyphenolsXia Wen
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA
Carcinogenesis 26:1774-81. 2005..Methoxylated dietary flavonoids, e.g. DMF and 3',4'-DMF, may be potent chemoprotectants by direct inhibition of CYP1B1/1A1 function and/or their protein expression... - Cellular uptake and efflux of the tea flavonoid (-)epicatechin-3-gallate in the human intestinal cell line Caco-2Jaya Bharathi Vaidyanathan
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 173 Ashley Avenue, P.O. Box 250505, Charleston, SC 29425, USA
J Pharmacol Exp Ther 307:745-52. 2003..Together, these observations demonstrate important roles of membrane transporters, i.e., MCT, MRP2, P-glycoprotein, and MRP1, in the cellular accumulation and potential effects of ECG... - Glucuronidation and sulfation of the tea flavonoid (-)-epicatechin by the human and rat enzymesJaya Bharathi Vaidyanathan
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston 29425, USA
Drug Metab Dispos 30:897-903. 2002..There was also a large species difference both in glucuronidation and sulfation of EC between rats and humans... - Flavonoid glycosides inhibit oral cancer cell proliferation--role of cellular uptake and hydrolysis to the aglyconesAlyson M Browning
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA
J Pharm Pharmacol 57:1037-42. 2005..In summary, dietary flavonoid glycosides may exert cellular effects in the oral cavity, but this varies greatly with the nature of the glycoside... - 5,7-Dimethoxyflavone downregulates CYP1A1 expression and benzo[a]pyrene-induced DNA binding in Hep G2 cellsXia Wen
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA
Carcinogenesis 26:803-9. 2005..In conclusion, DMF was a highly potent inhibitor of BaP-induced DNA binding and CYP1A1 protein expression and activity in the Hep G2 cells. These properties may make DMF an effective chemoprotectant in chemical-induced liver cancer... - Inhibition of benzo[a]pyrene-activating enzymes and DNA binding in human bronchial epithelial BEAS-2B cells by methoxylated flavonoidsPetra A Tsuji
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA
Carcinogenesis 27:1579-85. 2006.... - Cytochrome P450 1B1, a novel chemopreventive target for benzo[a]pyrene-initiated human esophageal cancerXia Wen
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA
Cancer Lett 246:109-14. 2007..Thus, dietary methoxylated flavones inhibited BaP-induced CYP1B1 transcription in a cell-specific manner and hold promise as chemopreventive agents in esophageal carcinogenesis... - Benzo[a]pyrene-induced cytochrome P450 1A and DNA binding in cultured trout hepatocytes - inhibition by plant polyphenolsPetra A Tsuji
Department of Cell and Molecular Pharmacology and Experimental Therapeutics Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA
Chem Biol Interact 169:25-31. 2007..However, extrapolation to human organs should be done cautiously... - Intestinal epithelial cell accumulation of the cancer preventive polyphenol ellagic acid--extensive binding to protein and DNAAlexander C Whitley
Department of Cellular and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 173 Ashley Avenue, PO Box 250505, Charleston, SC 29425, USA
Biochem Pharmacol 66:907-15. 2003..Thus, EA appears to accumulate selectively in the epithelial cells of the aerodigestive tract, where its cancer preventive actions may be displayed... - Accumulation and metabolism of the anticancer flavonoid 5,7-dimethoxyflavone compared to its unmethylated analog chrysin in the Atlantic killifishPetra A Tsuji
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, United States
Chem Biol Interact 164:85-92. 2006..In conclusion, our study demonstrated high tissue accumulation and limited metabolism of 5,7-DMF compared to chrysin in vivo, making this flavone a promising chemopreventive molecule... - Resveratrol transport and metabolism by human intestinal Caco-2 cellsMark I Kaldas
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA
J Pharm Pharmacol 55:307-12. 2003..Extensive accumulation of resveratrol in the Caco-2 cells, demonstrated in additional experiments, suggests enterocytes as a major target site for this cancer preventive agent... - Glucuronidation versus oxidation of the flavonoid galangin by human liver microsomes and hepatocytesYoko Otake
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, South Carolina 29425, USA
Drug Metab Dispos 30:576-81. 2002.... - Quercetin induces necrosis and apoptosis in SCC-9 oral cancer cellsMaricela Haghiac
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA
Nutr Cancer 53:220-31. 2005..Prolonged exposure of the surviving cells to quercetin causes apoptosis, presumably mediated by inhibition of TS protein... - Covalent binding of the flavonoid quercetin to human serum albuminMark I Kaldas
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, South Carolina, USA
J Agric Food Chem 53:4194-7. 2005..This provides further insights into the complex behavior of this major dietary flavonoid... - Oxidation of the flavonoids galangin and kaempferide by human liver microsomes and CYP1A1, CYP1A2, and CYP2C9Yoko Otake
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, South Carolina 29425, USA
Drug Metab Dispos 30:103-5. 2002..In addition, CYP1A1, although less efficient, was also able to oxidize the two flavonols. Thus, dietary flavonols are likely to undergo oxidative metabolism mainly in the liver but also extrahepatically... - Induction of human UDP-glucuronosyltransferase UGT1A1 by flavonoids-structural requirementsU Kristina Walle
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, South Carolina 29425, USA
Drug Metab Dispos 30:564-9. 2002..Together, these results strongly suggest that the flavonoid induction of UGT1A1 is through a novel nonaryl hydrocarbon receptor-mediated mechanism... - Aromatase inhibition by bioavailable methylated flavonesNga Ta
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA
J Steroid Biochem Mol Biol 107:127-9. 2007..Thus, some fully methylated flavones appear to have great potential as cancer chemopreventive/chemotherapeutic agents... - Cellular uptake of a radiolabelled analogue of neurotensin in the Caco-2 cell modelM Kyle Hadden
Department of Pharmaceutical Sciences, Medical University of South Carolina, 280 Calhoun Street, Charleston, South Carolina 29425, USA
J Pharm Pharmacol 57:327-33. 2005..Finally, after 60 min, intact *KK13 was identified associated with the cell components, providing further evidence for uptake and stability of the peptide... - Formation of transient covalent protein and DNA adducts by quercetin in cells with and without oxidative enzyme activityHester van der Woude
Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen, The Netherlands
Chem Res Toxicol 18:1907-16. 2005....
Research Grants
- FLAVONOID BIOAVAILABILITY IN HUMANS--CELLULAR STUDIESThomas Walle; Fiscal Year: 2002..In these studies we will in first hand seek to determine the bioavailability of flavonoid glycosides and their subsequent hydrolysis to aglycones in normal volunteers through plasma and urine determinations. ..
- FLAVONOID BIOAVAILABILITY IN HUMANS-CELLULAR STUDIESThomas Walle; Fiscal Year: 2005..The findings from the proposed studies should help us understand the bioavailability of the flavonoids, facilitating optimization of the chemopreventive utility of these natural or synthetic compounds. ..