Structure related effects of flavonoid aglycones on cell cycle progression of HepG2 cells

Metabolic activation of fisetin and quercetin by catechol-O-methyltransferase (COMT)

Miklós Poór, Zita Zrínyi, T. Kőszegi

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Dietary flavonoids are abundant in the Plant Kingdom and they are extensively studied because of their manifold pharmacological activities. Recent studies highlighted that cell cycle arrest plays a key role in their antiproliferative effect in different tumor cells. However, structure-activity relationship of flavonoids is poorly characterized. In our study the influence of 18 flavonoid aglycones (as well as two metabolites) on cell cycle distribution was investigated. Since flavonoids are extensively metabolized by liver cells, HepG2 tumor cell line was applied, considering the potential metabolic activation/inactivation of flavonoids. Our major observations are the followings: (1) Among the tested compounds diosmetin, fisetin, apigenin, lutelin, and quercetin provoked spectacular extent of G2/M phase cell cycle arrest. (2) Inhibition of catechol-O-methyltransferase enzyme by entacapone decreased the antiproliferative effects of fisetin and quercetin. (3) Geraldol and isorhamnetin (3′-O-methylated metabolites of fisetin and quercetin, respectively) demonstrated significantly higher antiproliferative effect on HepG2 cells compared to the parent compounds. Based on these results, O-methylated flavonoid metabolites or their chemically modified derivatives may be suitable candidates of tumor therapy in the future.

Original languageEnglish
Pages (from-to)998-1005
Number of pages8
JournalBiomedicine and Pharmacotherapy
Volume83
DOIs
Publication statusPublished - Oct 1 2016

Fingerprint

Catechol O-Methyltransferase
Quercetin
Hep G2 Cells
Flavonoids
Cell Cycle
M Phase Cell Cycle Checkpoints
Apigenin
G2 Phase
Structure-Activity Relationship
Cell Cycle Checkpoints
Tumor Cell Line
Metabolic Activation
fisetin
Neoplasms
Pharmacology
Liver
Enzymes

Keywords

  • Catechol-O-methyltransferase
  • Cell cycle arrest
  • Flavonoid aglycones
  • Geraldol
  • Isorhamnetin

ASJC Scopus subject areas

  • Pharmacology

Cite this

@article{90909191835448aab52b463347e98714,
title = "Structure related effects of flavonoid aglycones on cell cycle progression of HepG2 cells: Metabolic activation of fisetin and quercetin by catechol-O-methyltransferase (COMT)",
abstract = "Dietary flavonoids are abundant in the Plant Kingdom and they are extensively studied because of their manifold pharmacological activities. Recent studies highlighted that cell cycle arrest plays a key role in their antiproliferative effect in different tumor cells. However, structure-activity relationship of flavonoids is poorly characterized. In our study the influence of 18 flavonoid aglycones (as well as two metabolites) on cell cycle distribution was investigated. Since flavonoids are extensively metabolized by liver cells, HepG2 tumor cell line was applied, considering the potential metabolic activation/inactivation of flavonoids. Our major observations are the followings: (1) Among the tested compounds diosmetin, fisetin, apigenin, lutelin, and quercetin provoked spectacular extent of G2/M phase cell cycle arrest. (2) Inhibition of catechol-O-methyltransferase enzyme by entacapone decreased the antiproliferative effects of fisetin and quercetin. (3) Geraldol and isorhamnetin (3′-O-methylated metabolites of fisetin and quercetin, respectively) demonstrated significantly higher antiproliferative effect on HepG2 cells compared to the parent compounds. Based on these results, O-methylated flavonoid metabolites or their chemically modified derivatives may be suitable candidates of tumor therapy in the future.",
keywords = "Catechol-O-methyltransferase, Cell cycle arrest, Flavonoid aglycones, Geraldol, Isorhamnetin",
author = "Mikl{\'o}s Po{\'o}r and Zita Zr{\'i}nyi and T. Kőszegi",
year = "2016",
month = "10",
day = "1",
doi = "10.1016/j.biopha.2016.08.009",
language = "English",
volume = "83",
pages = "998--1005",
journal = "Biomedicine and Pharmacotherapy",
issn = "0753-3322",
publisher = "Elsevier Masson",

}

TY - JOUR

T1 - Structure related effects of flavonoid aglycones on cell cycle progression of HepG2 cells

T2 - Metabolic activation of fisetin and quercetin by catechol-O-methyltransferase (COMT)

AU - Poór, Miklós

AU - Zrínyi, Zita

AU - Kőszegi, T.

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Dietary flavonoids are abundant in the Plant Kingdom and they are extensively studied because of their manifold pharmacological activities. Recent studies highlighted that cell cycle arrest plays a key role in their antiproliferative effect in different tumor cells. However, structure-activity relationship of flavonoids is poorly characterized. In our study the influence of 18 flavonoid aglycones (as well as two metabolites) on cell cycle distribution was investigated. Since flavonoids are extensively metabolized by liver cells, HepG2 tumor cell line was applied, considering the potential metabolic activation/inactivation of flavonoids. Our major observations are the followings: (1) Among the tested compounds diosmetin, fisetin, apigenin, lutelin, and quercetin provoked spectacular extent of G2/M phase cell cycle arrest. (2) Inhibition of catechol-O-methyltransferase enzyme by entacapone decreased the antiproliferative effects of fisetin and quercetin. (3) Geraldol and isorhamnetin (3′-O-methylated metabolites of fisetin and quercetin, respectively) demonstrated significantly higher antiproliferative effect on HepG2 cells compared to the parent compounds. Based on these results, O-methylated flavonoid metabolites or their chemically modified derivatives may be suitable candidates of tumor therapy in the future.

AB - Dietary flavonoids are abundant in the Plant Kingdom and they are extensively studied because of their manifold pharmacological activities. Recent studies highlighted that cell cycle arrest plays a key role in their antiproliferative effect in different tumor cells. However, structure-activity relationship of flavonoids is poorly characterized. In our study the influence of 18 flavonoid aglycones (as well as two metabolites) on cell cycle distribution was investigated. Since flavonoids are extensively metabolized by liver cells, HepG2 tumor cell line was applied, considering the potential metabolic activation/inactivation of flavonoids. Our major observations are the followings: (1) Among the tested compounds diosmetin, fisetin, apigenin, lutelin, and quercetin provoked spectacular extent of G2/M phase cell cycle arrest. (2) Inhibition of catechol-O-methyltransferase enzyme by entacapone decreased the antiproliferative effects of fisetin and quercetin. (3) Geraldol and isorhamnetin (3′-O-methylated metabolites of fisetin and quercetin, respectively) demonstrated significantly higher antiproliferative effect on HepG2 cells compared to the parent compounds. Based on these results, O-methylated flavonoid metabolites or their chemically modified derivatives may be suitable candidates of tumor therapy in the future.

KW - Catechol-O-methyltransferase

KW - Cell cycle arrest

KW - Flavonoid aglycones

KW - Geraldol

KW - Isorhamnetin

UR - http://www.scopus.com/inward/record.url?scp=84981313885&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84981313885&partnerID=8YFLogxK

U2 - 10.1016/j.biopha.2016.08.009

DO - 10.1016/j.biopha.2016.08.009

M3 - Article

VL - 83

SP - 998

EP - 1005

JO - Biomedicine and Pharmacotherapy

JF - Biomedicine and Pharmacotherapy

SN - 0753-3322

ER -