Induction of UDP-glucuronosyltransferase 1A by naturally occurring phytochemicals in human hepatoma cells

UDP-glucuronosyltransferases (UGTs) are important detoxification and drug-metabolizing enzymes, which catalyse the glucuronidation of exogenous and endogenous chemicals. The anti-carcinogenic activity of dietary phytochemicals is partly attributed to the induction of phase II enzymes, including UGT1...

Full description

Bibliographic Details
Main Authors: Violetta Krajka-Kuźniak, Adam Krysztofiak, Jarosław Paluszczak
Format: Article
Language:English
Published: Poznan University of Medical Sciences 2014-09-01
Series:Journal of Medical Science
Subjects:
Online Access:https://jms.ump.edu.pl/index.php/JMS/article/view/69
_version_ 1819135617636761600
author Violetta Krajka-Kuźniak
Adam Krysztofiak
Jarosław Paluszczak
author_facet Violetta Krajka-Kuźniak
Adam Krysztofiak
Jarosław Paluszczak
author_sort Violetta Krajka-Kuźniak
collection DOAJ
description UDP-glucuronosyltransferases (UGTs) are important detoxification and drug-metabolizing enzymes, which catalyse the glucuronidation of exogenous and endogenous chemicals. The anti-carcinogenic activity of dietary phytochemicals is partly attributed to the induction of phase II enzymes, including UGT1A. Our earlier study showed that protocatechuic acid increased UGT activity in rat liver. A similar effect was observed for indole-3-carbinol and phenethyl isothiocyanate in rat liver. In this study we assessed the effect of protocatechuic acid, tannic acid, indole-3-carbinol and phenethyl isothiocyanate on the expression and protein level of UGT1A in hepatocellular carcinoma HepG2 cells. Cells were incubated with 2µM and 10µM of protocatechuic acid, tannic acid, or indole-3-carbinol and 1µM and 5µM of phenethyl isothiocyanate for 72 hours. Transcript level was measured by RT-PCR and protein level by the immunoblot assay. Treatment with protocatechuic acid, tannic acid, indole-3-carbinol and phenethyl isothiocyanate induced the expression and protein level of UGT1A. Phenethyl isothiocyanate increased the mRNA of UGT1A to the most extent (0.28–5.7 fold change, p < 0.05). Increased expression of UGT1A was accompanied by the enhancement of its protein level, with the exception of protocatechuic acid at the dose of 2µM. Overall, isothiocyanates and indoles were more potent as UGT inducers than phenolic acids. Collectively, the results suggest that the induction of UGT1A could contribute to the hepatoprotective and chemopreventive properties of these phytochemicals.
first_indexed 2024-12-22T10:21:56Z
format Article
id doaj.art-9c878b110e294a1c9c5a209c39988667
institution Directory Open Access Journal
issn 2353-9798
2353-9801
language English
last_indexed 2024-12-22T10:21:56Z
publishDate 2014-09-01
publisher Poznan University of Medical Sciences
record_format Article
series Journal of Medical Science
spelling doaj.art-9c878b110e294a1c9c5a209c399886672022-12-21T18:29:36ZengPoznan University of Medical SciencesJournal of Medical Science2353-97982353-98012014-09-0183310.20883/medical.e69Induction of UDP-glucuronosyltransferase 1A by naturally occurring phytochemicals in human hepatoma cellsVioletta Krajka-Kuźniak0Adam Krysztofiak1Jarosław Paluszczak2Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, PolandDepartment of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, PolandDepartment of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, PolandUDP-glucuronosyltransferases (UGTs) are important detoxification and drug-metabolizing enzymes, which catalyse the glucuronidation of exogenous and endogenous chemicals. The anti-carcinogenic activity of dietary phytochemicals is partly attributed to the induction of phase II enzymes, including UGT1A. Our earlier study showed that protocatechuic acid increased UGT activity in rat liver. A similar effect was observed for indole-3-carbinol and phenethyl isothiocyanate in rat liver. In this study we assessed the effect of protocatechuic acid, tannic acid, indole-3-carbinol and phenethyl isothiocyanate on the expression and protein level of UGT1A in hepatocellular carcinoma HepG2 cells. Cells were incubated with 2µM and 10µM of protocatechuic acid, tannic acid, or indole-3-carbinol and 1µM and 5µM of phenethyl isothiocyanate for 72 hours. Transcript level was measured by RT-PCR and protein level by the immunoblot assay. Treatment with protocatechuic acid, tannic acid, indole-3-carbinol and phenethyl isothiocyanate induced the expression and protein level of UGT1A. Phenethyl isothiocyanate increased the mRNA of UGT1A to the most extent (0.28–5.7 fold change, p < 0.05). Increased expression of UGT1A was accompanied by the enhancement of its protein level, with the exception of protocatechuic acid at the dose of 2µM. Overall, isothiocyanates and indoles were more potent as UGT inducers than phenolic acids. Collectively, the results suggest that the induction of UGT1A could contribute to the hepatoprotective and chemopreventive properties of these phytochemicals.https://jms.ump.edu.pl/index.php/JMS/article/view/69tannic acidprotocatechuic acidindole-3-carbinolphenethyl isothiocyanateUGT1AHepG2
spellingShingle Violetta Krajka-Kuźniak
Adam Krysztofiak
Jarosław Paluszczak
Induction of UDP-glucuronosyltransferase 1A by naturally occurring phytochemicals in human hepatoma cells
Journal of Medical Science
tannic acid
protocatechuic acid
indole-3-carbinol
phenethyl isothiocyanate
UGT1A
HepG2
title Induction of UDP-glucuronosyltransferase 1A by naturally occurring phytochemicals in human hepatoma cells
title_full Induction of UDP-glucuronosyltransferase 1A by naturally occurring phytochemicals in human hepatoma cells
title_fullStr Induction of UDP-glucuronosyltransferase 1A by naturally occurring phytochemicals in human hepatoma cells
title_full_unstemmed Induction of UDP-glucuronosyltransferase 1A by naturally occurring phytochemicals in human hepatoma cells
title_short Induction of UDP-glucuronosyltransferase 1A by naturally occurring phytochemicals in human hepatoma cells
title_sort induction of udp glucuronosyltransferase 1a by naturally occurring phytochemicals in human hepatoma cells
topic tannic acid
protocatechuic acid
indole-3-carbinol
phenethyl isothiocyanate
UGT1A
HepG2
url https://jms.ump.edu.pl/index.php/JMS/article/view/69
work_keys_str_mv AT violettakrajkakuzniak inductionofudpglucuronosyltransferase1abynaturallyoccurringphytochemicalsinhumanhepatomacells
AT adamkrysztofiak inductionofudpglucuronosyltransferase1abynaturallyoccurringphytochemicalsinhumanhepatomacells
AT jarosławpaluszczak inductionofudpglucuronosyltransferase1abynaturallyoccurringphytochemicalsinhumanhepatomacells