Tricetin suppresses the migration/invasion of human glioblastoma multiforme cells by inhibiting matrix metalloproteinase-2 through modulation of the expression and transcriptional activity of specificity protein 1

Rockey Chao, Jyh Ming Chow, Yi Hsien Hsieh, Chi Kuan Chen, Wei Jiunn Lee, Feng Koo Hsieh, Nuo Yi Yu, Ming Chih Chou, Chao Wen Cheng, Shun Fa Yang, Ming Hsien Chien

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12 Citations (Scopus)

Abstract

Objective: Glioblastoma multiforme (GBM) is a severely invasive tumor that can be fatal because it is difficult to treat. Tricetin, a natural flavonoid, was demonstrated to inhibit the growth of various cancers, but the effect of tricetin on cancer motility is largely unknown.Research design and methods: In the present study, we examined the anti-invasive properties of tricetin in huwman GBM cells.Results: Our results showed that tricetin inhibited the migration/invasion of two GBM cell lines. We found that tricetin inhibited MMP-2 expression in the GBM cells. Real-time polymerase chain reaction and promoter activity assays indicated that tricetin inhibited MMP-2 expression at the transcriptional level. Such inhibitory effects were associated with the suppression of specificity protein-1 (SP-1) DNA-binding activity. An examination of clinical samples revealed a positive correlation between SP-1 and MMP-2 in glioma specimens, and higher expression levels were correlated with a worse probability of survival. Moreover, blocking the extracellular signal-regulated kinase (ERK) pathway also inhibited MMP-2-mediated cell motility, and further enhanced the anti-invasive ability of tricetin in GBM cells.Conclusions: SP-1 is an important target of tricetin for suppressing MMP-2-mediated cell motility in GBM cells, and a combination of tricetin and an ERK inhibitor may be a good strategy for preventing GBM invasion.

Original languageEnglish
Pages (from-to)1293-1306
Number of pages14
JournalExpert Opinion on Therapeutic Targets
Volume19
Issue number10
DOIs
Publication statusPublished - Oct 3 2015

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Matrix Metalloproteinase 2
Glioblastoma
Modulation
Matrix Metalloproteinases
Proteins
Extracellular Signal-Regulated MAP Kinases
Cell Movement
tricetin
Neoplasms
Polymerase chain reaction
DNA-Binding Proteins
Flavonoids
Glioma
Tumors
Real-Time Polymerase Chain Reaction
Assays
Research Design
Cells
Cell Line
Survival

Keywords

  • extracellular signal-regulated kinase
  • glioblastoma
  • invasion
  • matrix metalloproteinases-2
  • specificity protein-1
  • tricetin

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Clinical Biochemistry
  • Molecular Medicine

Cite this

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title = "Tricetin suppresses the migration/invasion of human glioblastoma multiforme cells by inhibiting matrix metalloproteinase-2 through modulation of the expression and transcriptional activity of specificity protein 1",
abstract = "Objective: Glioblastoma multiforme (GBM) is a severely invasive tumor that can be fatal because it is difficult to treat. Tricetin, a natural flavonoid, was demonstrated to inhibit the growth of various cancers, but the effect of tricetin on cancer motility is largely unknown.Research design and methods: In the present study, we examined the anti-invasive properties of tricetin in huwman GBM cells.Results: Our results showed that tricetin inhibited the migration/invasion of two GBM cell lines. We found that tricetin inhibited MMP-2 expression in the GBM cells. Real-time polymerase chain reaction and promoter activity assays indicated that tricetin inhibited MMP-2 expression at the transcriptional level. Such inhibitory effects were associated with the suppression of specificity protein-1 (SP-1) DNA-binding activity. An examination of clinical samples revealed a positive correlation between SP-1 and MMP-2 in glioma specimens, and higher expression levels were correlated with a worse probability of survival. Moreover, blocking the extracellular signal-regulated kinase (ERK) pathway also inhibited MMP-2-mediated cell motility, and further enhanced the anti-invasive ability of tricetin in GBM cells.Conclusions: SP-1 is an important target of tricetin for suppressing MMP-2-mediated cell motility in GBM cells, and a combination of tricetin and an ERK inhibitor may be a good strategy for preventing GBM invasion.",
keywords = "extracellular signal-regulated kinase, glioblastoma, invasion, matrix metalloproteinases-2, specificity protein-1, tricetin",
author = "Rockey Chao and Chow, {Jyh Ming} and Hsieh, {Yi Hsien} and Chen, {Chi Kuan} and Lee, {Wei Jiunn} and Hsieh, {Feng Koo} and Yu, {Nuo Yi} and Chou, {Ming Chih} and Cheng, {Chao Wen} and Yang, {Shun Fa} and Chien, {Ming Hsien}",
year = "2015",
month = "10",
day = "3",
doi = "10.1517/14728222.2015.1075509",
language = "English",
volume = "19",
pages = "1293--1306",
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TY - JOUR

T1 - Tricetin suppresses the migration/invasion of human glioblastoma multiforme cells by inhibiting matrix metalloproteinase-2 through modulation of the expression and transcriptional activity of specificity protein 1

AU - Chao, Rockey

AU - Chow, Jyh Ming

AU - Hsieh, Yi Hsien

AU - Chen, Chi Kuan

AU - Lee, Wei Jiunn

AU - Hsieh, Feng Koo

AU - Yu, Nuo Yi

AU - Chou, Ming Chih

AU - Cheng, Chao Wen

AU - Yang, Shun Fa

AU - Chien, Ming Hsien

PY - 2015/10/3

Y1 - 2015/10/3

N2 - Objective: Glioblastoma multiforme (GBM) is a severely invasive tumor that can be fatal because it is difficult to treat. Tricetin, a natural flavonoid, was demonstrated to inhibit the growth of various cancers, but the effect of tricetin on cancer motility is largely unknown.Research design and methods: In the present study, we examined the anti-invasive properties of tricetin in huwman GBM cells.Results: Our results showed that tricetin inhibited the migration/invasion of two GBM cell lines. We found that tricetin inhibited MMP-2 expression in the GBM cells. Real-time polymerase chain reaction and promoter activity assays indicated that tricetin inhibited MMP-2 expression at the transcriptional level. Such inhibitory effects were associated with the suppression of specificity protein-1 (SP-1) DNA-binding activity. An examination of clinical samples revealed a positive correlation between SP-1 and MMP-2 in glioma specimens, and higher expression levels were correlated with a worse probability of survival. Moreover, blocking the extracellular signal-regulated kinase (ERK) pathway also inhibited MMP-2-mediated cell motility, and further enhanced the anti-invasive ability of tricetin in GBM cells.Conclusions: SP-1 is an important target of tricetin for suppressing MMP-2-mediated cell motility in GBM cells, and a combination of tricetin and an ERK inhibitor may be a good strategy for preventing GBM invasion.

AB - Objective: Glioblastoma multiforme (GBM) is a severely invasive tumor that can be fatal because it is difficult to treat. Tricetin, a natural flavonoid, was demonstrated to inhibit the growth of various cancers, but the effect of tricetin on cancer motility is largely unknown.Research design and methods: In the present study, we examined the anti-invasive properties of tricetin in huwman GBM cells.Results: Our results showed that tricetin inhibited the migration/invasion of two GBM cell lines. We found that tricetin inhibited MMP-2 expression in the GBM cells. Real-time polymerase chain reaction and promoter activity assays indicated that tricetin inhibited MMP-2 expression at the transcriptional level. Such inhibitory effects were associated with the suppression of specificity protein-1 (SP-1) DNA-binding activity. An examination of clinical samples revealed a positive correlation between SP-1 and MMP-2 in glioma specimens, and higher expression levels were correlated with a worse probability of survival. Moreover, blocking the extracellular signal-regulated kinase (ERK) pathway also inhibited MMP-2-mediated cell motility, and further enhanced the anti-invasive ability of tricetin in GBM cells.Conclusions: SP-1 is an important target of tricetin for suppressing MMP-2-mediated cell motility in GBM cells, and a combination of tricetin and an ERK inhibitor may be a good strategy for preventing GBM invasion.

KW - extracellular signal-regulated kinase

KW - glioblastoma

KW - invasion

KW - matrix metalloproteinases-2

KW - specificity protein-1

KW - tricetin

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SN - 1472-8222

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