151 Citations (Scopus)

Abstract

Quercetin (QUE; 3,5,7,3′,4′-tetrahydroxyflavone) has been shown to possess several beneficial biological activities including antitumor, anti-inflammation and antioxidant properties; however, the effects of QUE in preventing invasion by breast carcinoma cells are still undefined. Increases in the protein, messenger RNA and enzyme activity levels of matrix metalloproteinase (MMP)-9 were observed in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated MCF-7 cells, and these were blocked by QUE, but not by quercitrin or rutin. A translocation of protein kinase C (PKC)δ from the cytosol to the membrane followed by activation of extracellular signal-regulated kinase (ERK) and c-Jun/activator protein-1 (AP-1) by TPA was demonstrated, and TPA-induced MMP-9 activation and migration were inhibited by the pan PKC inhibitor, GF109203X, the specific PKCδ inhibitor, rottlerin, an ERK inhibitor (PD98059) and an AP-1 inhibitor (curcumin). Application of QUE significantly suppressed TPA-induced activation of the PKCδ/ ERK/AP-1-signaling cascade. To elucidate the importance of hydroxyl (OH) substitutions to QUE's inhibition of tumor migration, several structurally related flavones of QUE including 3′,4′-diOH, 3′,4′-diOCH3, 3,5,7-triOH, 3,4′,4′-triOH, 3,3′,4′-triOCH3, luteolin and fisetin were used. Results suggested that OH groups at both C3′ and C4′ play central roles in QUE's inhibition of TPA-induced MMP-9 activation and migration, and an additional OH at C3, C5 or C7 may increase the inhibitory potency of the 3′,4′-diOH flavone against TPA-induced MMP-9 activity and migration. The antitumor invasion and migration effects of breast carcinoma cells induced by QUE with the structure-activity relationship analysis were identified.

Original languageEnglish
Pages (from-to)1807-1815
Number of pages9
JournalCarcinogenesis
Volume29
Issue number9
DOIs
Publication statusPublished - 2008

Fingerprint

Proto-Oncogene Proteins c-jun
Quercetin
Extracellular Signal-Regulated MAP Kinases
Matrix Metalloproteinase 9
Transcription Factor AP-1
Tetradecanoylphorbol Acetate
Protein Kinase C
Breast Neoplasms
Hydroxyl Radical
Neoplasms
flavone
Protein C Inhibitor
Protein Kinase Inhibitors
Flavones
Luteolin
Rutin
Curcumin
MCF-7 Cells
Structure-Activity Relationship
Cytosol

ASJC Scopus subject areas

  • Cancer Research

Cite this

@article{5a98827d21704f4abc0c671664e6ef21,
title = "Quercetin inhibition of tumor invasion via suppressing PKCδ/ERK/ AP-1-dependent matrix metalloproteinase-9 activation in breast carcinoma cells",
abstract = "Quercetin (QUE; 3,5,7,3′,4′-tetrahydroxyflavone) has been shown to possess several beneficial biological activities including antitumor, anti-inflammation and antioxidant properties; however, the effects of QUE in preventing invasion by breast carcinoma cells are still undefined. Increases in the protein, messenger RNA and enzyme activity levels of matrix metalloproteinase (MMP)-9 were observed in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated MCF-7 cells, and these were blocked by QUE, but not by quercitrin or rutin. A translocation of protein kinase C (PKC)δ from the cytosol to the membrane followed by activation of extracellular signal-regulated kinase (ERK) and c-Jun/activator protein-1 (AP-1) by TPA was demonstrated, and TPA-induced MMP-9 activation and migration were inhibited by the pan PKC inhibitor, GF109203X, the specific PKCδ inhibitor, rottlerin, an ERK inhibitor (PD98059) and an AP-1 inhibitor (curcumin). Application of QUE significantly suppressed TPA-induced activation of the PKCδ/ ERK/AP-1-signaling cascade. To elucidate the importance of hydroxyl (OH) substitutions to QUE's inhibition of tumor migration, several structurally related flavones of QUE including 3′,4′-diOH, 3′,4′-diOCH3, 3,5,7-triOH, 3,4′,4′-triOH, 3,3′,4′-triOCH3, luteolin and fisetin were used. Results suggested that OH groups at both C3′ and C4′ play central roles in QUE's inhibition of TPA-induced MMP-9 activation and migration, and an additional OH at C3, C5 or C7 may increase the inhibitory potency of the 3′,4′-diOH flavone against TPA-induced MMP-9 activity and migration. The antitumor invasion and migration effects of breast carcinoma cells induced by QUE with the structure-activity relationship analysis were identified.",
author = "Lin, {Cheng Wei} and Hou, {Wen Chi} and Shen, {Shing Chuan} and Juan, {Shu Hui} and Ko, {Ching Huai} and Wang, {Ling Mei} and Chen, {Yen Chou}",
year = "2008",
doi = "10.1093/carcin/bgn162",
language = "English",
volume = "29",
pages = "1807--1815",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "9",

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TY - JOUR

T1 - Quercetin inhibition of tumor invasion via suppressing PKCδ/ERK/ AP-1-dependent matrix metalloproteinase-9 activation in breast carcinoma cells

AU - Lin, Cheng Wei

AU - Hou, Wen Chi

AU - Shen, Shing Chuan

AU - Juan, Shu Hui

AU - Ko, Ching Huai

AU - Wang, Ling Mei

AU - Chen, Yen Chou

PY - 2008

Y1 - 2008

N2 - Quercetin (QUE; 3,5,7,3′,4′-tetrahydroxyflavone) has been shown to possess several beneficial biological activities including antitumor, anti-inflammation and antioxidant properties; however, the effects of QUE in preventing invasion by breast carcinoma cells are still undefined. Increases in the protein, messenger RNA and enzyme activity levels of matrix metalloproteinase (MMP)-9 were observed in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated MCF-7 cells, and these were blocked by QUE, but not by quercitrin or rutin. A translocation of protein kinase C (PKC)δ from the cytosol to the membrane followed by activation of extracellular signal-regulated kinase (ERK) and c-Jun/activator protein-1 (AP-1) by TPA was demonstrated, and TPA-induced MMP-9 activation and migration were inhibited by the pan PKC inhibitor, GF109203X, the specific PKCδ inhibitor, rottlerin, an ERK inhibitor (PD98059) and an AP-1 inhibitor (curcumin). Application of QUE significantly suppressed TPA-induced activation of the PKCδ/ ERK/AP-1-signaling cascade. To elucidate the importance of hydroxyl (OH) substitutions to QUE's inhibition of tumor migration, several structurally related flavones of QUE including 3′,4′-diOH, 3′,4′-diOCH3, 3,5,7-triOH, 3,4′,4′-triOH, 3,3′,4′-triOCH3, luteolin and fisetin were used. Results suggested that OH groups at both C3′ and C4′ play central roles in QUE's inhibition of TPA-induced MMP-9 activation and migration, and an additional OH at C3, C5 or C7 may increase the inhibitory potency of the 3′,4′-diOH flavone against TPA-induced MMP-9 activity and migration. The antitumor invasion and migration effects of breast carcinoma cells induced by QUE with the structure-activity relationship analysis were identified.

AB - Quercetin (QUE; 3,5,7,3′,4′-tetrahydroxyflavone) has been shown to possess several beneficial biological activities including antitumor, anti-inflammation and antioxidant properties; however, the effects of QUE in preventing invasion by breast carcinoma cells are still undefined. Increases in the protein, messenger RNA and enzyme activity levels of matrix metalloproteinase (MMP)-9 were observed in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated MCF-7 cells, and these were blocked by QUE, but not by quercitrin or rutin. A translocation of protein kinase C (PKC)δ from the cytosol to the membrane followed by activation of extracellular signal-regulated kinase (ERK) and c-Jun/activator protein-1 (AP-1) by TPA was demonstrated, and TPA-induced MMP-9 activation and migration were inhibited by the pan PKC inhibitor, GF109203X, the specific PKCδ inhibitor, rottlerin, an ERK inhibitor (PD98059) and an AP-1 inhibitor (curcumin). Application of QUE significantly suppressed TPA-induced activation of the PKCδ/ ERK/AP-1-signaling cascade. To elucidate the importance of hydroxyl (OH) substitutions to QUE's inhibition of tumor migration, several structurally related flavones of QUE including 3′,4′-diOH, 3′,4′-diOCH3, 3,5,7-triOH, 3,4′,4′-triOH, 3,3′,4′-triOCH3, luteolin and fisetin were used. Results suggested that OH groups at both C3′ and C4′ play central roles in QUE's inhibition of TPA-induced MMP-9 activation and migration, and an additional OH at C3, C5 or C7 may increase the inhibitory potency of the 3′,4′-diOH flavone against TPA-induced MMP-9 activity and migration. The antitumor invasion and migration effects of breast carcinoma cells induced by QUE with the structure-activity relationship analysis were identified.

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U2 - 10.1093/carcin/bgn162

DO - 10.1093/carcin/bgn162

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