Resveratrol inhibits human lung adenocarcinoma cell metastasis by suppressing heme oxygenase 1-mediated nuclear factor-κB pathway and subsequently downregulating expression of matrix metalloproteinases

Po Len Liu, Jong Rung Tsai, Albert Linton Charles, Jhi Jhu Hwang, Shah Hwa Chou, Yueh Hsin Ping, Feng Yen Lin, Yuh Lien Chen, Chun Ying Hung, Wen Chi Chen, Yung Hsiang Chen, Inn Wen Chong

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

Resveratrol exhibits potential anti-carcinogenic activities. Heme oxygenase-1 (HO-1) is involved in angiogenesis and tumor metastasis. Matrix metalloproteinases (MMPs) are key enzymes in the degradation of extracellular matrix, and their expression may be dysregulated in lung cancer metastasis. In this study, we investigated the anti-invasive mechanism of resveratrol in lung cancer cells. HO-1 was shown to be elevated (~4.7-fold) in lung cancer tumor samples as compared with matched normal tissues. After treatment of lung adenocarcinoma cell line A549 cells with resveratrol (50μM) for 24h, the migratory and invasive abilities (38 and 30% inhibition, respectively) of A549 cells were significantly reduced. Resveratrol significantly inhibited HO-1-mediated MMP-9 (35% inhibition) and MMP-2 (28% inhibition) expression in lung cancer cells. Nuclear factor (NF)-κB inhibitor induced a marked reduction in MMP-9 and MMP-2 expression, suggesting NF-κB pathway could play an important role. Furthermore, HO-1 inhibition and silencing significantly suppressed MMPs and invasion of lung cancer cells. Our results suggest that resveratrol inhibited HO-1 and subsequently MMP-9 and MMP-2 expression in lung cancer cells. The inhibitory effects of resveratrol on MMP expression and invasion of lung cancer cells are, in part, associated with the HO-1-mediated NF-κB pathway.

Original languageEnglish
JournalMolecular Nutrition and Food Research
Volume54
Issue numberSUPPL. 2
DOIs
Publication statusPublished - Jul 2010

Fingerprint

heme oxygenase (biliverdin-producing)
Heme Oxygenase-1
resveratrol
metalloproteinases
lung neoplasms
adenocarcinoma
Matrix Metalloproteinases
metastasis
Lung Neoplasms
Down-Regulation
lungs
Neoplasm Metastasis
gelatinase A
gelatinase B
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
cells
neoplasms
anticarcinogenic activity
angiogenesis

Keywords

  • Heme oxygenase 1
  • Matrix metalloproteinase
  • Metastasis
  • Non-small cell lung cancer
  • Resveratrol

ASJC Scopus subject areas

  • Food Science
  • Biotechnology

Cite this

Resveratrol inhibits human lung adenocarcinoma cell metastasis by suppressing heme oxygenase 1-mediated nuclear factor-κB pathway and subsequently downregulating expression of matrix metalloproteinases. / Liu, Po Len; Tsai, Jong Rung; Charles, Albert Linton; Hwang, Jhi Jhu; Chou, Shah Hwa; Ping, Yueh Hsin; Lin, Feng Yen; Chen, Yuh Lien; Hung, Chun Ying; Chen, Wen Chi; Chen, Yung Hsiang; Chong, Inn Wen.

In: Molecular Nutrition and Food Research, Vol. 54, No. SUPPL. 2, 07.2010.

Research output: Contribution to journalArticle

Liu, Po Len ; Tsai, Jong Rung ; Charles, Albert Linton ; Hwang, Jhi Jhu ; Chou, Shah Hwa ; Ping, Yueh Hsin ; Lin, Feng Yen ; Chen, Yuh Lien ; Hung, Chun Ying ; Chen, Wen Chi ; Chen, Yung Hsiang ; Chong, Inn Wen. / Resveratrol inhibits human lung adenocarcinoma cell metastasis by suppressing heme oxygenase 1-mediated nuclear factor-κB pathway and subsequently downregulating expression of matrix metalloproteinases. In: Molecular Nutrition and Food Research. 2010 ; Vol. 54, No. SUPPL. 2.
@article{cbc9e205159d432095f0bfee8f87156a,
title = "Resveratrol inhibits human lung adenocarcinoma cell metastasis by suppressing heme oxygenase 1-mediated nuclear factor-κB pathway and subsequently downregulating expression of matrix metalloproteinases",
abstract = "Resveratrol exhibits potential anti-carcinogenic activities. Heme oxygenase-1 (HO-1) is involved in angiogenesis and tumor metastasis. Matrix metalloproteinases (MMPs) are key enzymes in the degradation of extracellular matrix, and their expression may be dysregulated in lung cancer metastasis. In this study, we investigated the anti-invasive mechanism of resveratrol in lung cancer cells. HO-1 was shown to be elevated (~4.7-fold) in lung cancer tumor samples as compared with matched normal tissues. After treatment of lung adenocarcinoma cell line A549 cells with resveratrol (50μM) for 24h, the migratory and invasive abilities (38 and 30{\%} inhibition, respectively) of A549 cells were significantly reduced. Resveratrol significantly inhibited HO-1-mediated MMP-9 (35{\%} inhibition) and MMP-2 (28{\%} inhibition) expression in lung cancer cells. Nuclear factor (NF)-κB inhibitor induced a marked reduction in MMP-9 and MMP-2 expression, suggesting NF-κB pathway could play an important role. Furthermore, HO-1 inhibition and silencing significantly suppressed MMPs and invasion of lung cancer cells. Our results suggest that resveratrol inhibited HO-1 and subsequently MMP-9 and MMP-2 expression in lung cancer cells. The inhibitory effects of resveratrol on MMP expression and invasion of lung cancer cells are, in part, associated with the HO-1-mediated NF-κB pathway.",
keywords = "Heme oxygenase 1, Matrix metalloproteinase, Metastasis, Non-small cell lung cancer, Resveratrol",
author = "Liu, {Po Len} and Tsai, {Jong Rung} and Charles, {Albert Linton} and Hwang, {Jhi Jhu} and Chou, {Shah Hwa} and Ping, {Yueh Hsin} and Lin, {Feng Yen} and Chen, {Yuh Lien} and Hung, {Chun Ying} and Chen, {Wen Chi} and Chen, {Yung Hsiang} and Chong, {Inn Wen}",
year = "2010",
month = "7",
doi = "10.1002/mnfr.200900550",
language = "English",
volume = "54",
journal = "Molecular Nutrition and Food Research",
issn = "1613-4125",
publisher = "Wiley-VCH Verlag",
number = "SUPPL. 2",

}

TY - JOUR

T1 - Resveratrol inhibits human lung adenocarcinoma cell metastasis by suppressing heme oxygenase 1-mediated nuclear factor-κB pathway and subsequently downregulating expression of matrix metalloproteinases

AU - Liu, Po Len

AU - Tsai, Jong Rung

AU - Charles, Albert Linton

AU - Hwang, Jhi Jhu

AU - Chou, Shah Hwa

AU - Ping, Yueh Hsin

AU - Lin, Feng Yen

AU - Chen, Yuh Lien

AU - Hung, Chun Ying

AU - Chen, Wen Chi

AU - Chen, Yung Hsiang

AU - Chong, Inn Wen

PY - 2010/7

Y1 - 2010/7

N2 - Resveratrol exhibits potential anti-carcinogenic activities. Heme oxygenase-1 (HO-1) is involved in angiogenesis and tumor metastasis. Matrix metalloproteinases (MMPs) are key enzymes in the degradation of extracellular matrix, and their expression may be dysregulated in lung cancer metastasis. In this study, we investigated the anti-invasive mechanism of resveratrol in lung cancer cells. HO-1 was shown to be elevated (~4.7-fold) in lung cancer tumor samples as compared with matched normal tissues. After treatment of lung adenocarcinoma cell line A549 cells with resveratrol (50μM) for 24h, the migratory and invasive abilities (38 and 30% inhibition, respectively) of A549 cells were significantly reduced. Resveratrol significantly inhibited HO-1-mediated MMP-9 (35% inhibition) and MMP-2 (28% inhibition) expression in lung cancer cells. Nuclear factor (NF)-κB inhibitor induced a marked reduction in MMP-9 and MMP-2 expression, suggesting NF-κB pathway could play an important role. Furthermore, HO-1 inhibition and silencing significantly suppressed MMPs and invasion of lung cancer cells. Our results suggest that resveratrol inhibited HO-1 and subsequently MMP-9 and MMP-2 expression in lung cancer cells. The inhibitory effects of resveratrol on MMP expression and invasion of lung cancer cells are, in part, associated with the HO-1-mediated NF-κB pathway.

AB - Resveratrol exhibits potential anti-carcinogenic activities. Heme oxygenase-1 (HO-1) is involved in angiogenesis and tumor metastasis. Matrix metalloproteinases (MMPs) are key enzymes in the degradation of extracellular matrix, and their expression may be dysregulated in lung cancer metastasis. In this study, we investigated the anti-invasive mechanism of resveratrol in lung cancer cells. HO-1 was shown to be elevated (~4.7-fold) in lung cancer tumor samples as compared with matched normal tissues. After treatment of lung adenocarcinoma cell line A549 cells with resveratrol (50μM) for 24h, the migratory and invasive abilities (38 and 30% inhibition, respectively) of A549 cells were significantly reduced. Resveratrol significantly inhibited HO-1-mediated MMP-9 (35% inhibition) and MMP-2 (28% inhibition) expression in lung cancer cells. Nuclear factor (NF)-κB inhibitor induced a marked reduction in MMP-9 and MMP-2 expression, suggesting NF-κB pathway could play an important role. Furthermore, HO-1 inhibition and silencing significantly suppressed MMPs and invasion of lung cancer cells. Our results suggest that resveratrol inhibited HO-1 and subsequently MMP-9 and MMP-2 expression in lung cancer cells. The inhibitory effects of resveratrol on MMP expression and invasion of lung cancer cells are, in part, associated with the HO-1-mediated NF-κB pathway.

KW - Heme oxygenase 1

KW - Matrix metalloproteinase

KW - Metastasis

KW - Non-small cell lung cancer

KW - Resveratrol

UR - http://www.scopus.com/inward/record.url?scp=77957590701&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77957590701&partnerID=8YFLogxK

U2 - 10.1002/mnfr.200900550

DO - 10.1002/mnfr.200900550

M3 - Article

C2 - 20461740

AN - SCOPUS:77957590701

VL - 54

JO - Molecular Nutrition and Food Research

JF - Molecular Nutrition and Food Research

SN - 1613-4125

IS - SUPPL. 2

ER -