Piceatannol inhibits MMP-9-dependent invasion of tumor necrosis factor-α-stimulated DU145 cells by suppressing the Akt-mediated nuclear factor-κB pathway

Rajapaksha Gendara Prasad Tharanga Jayasooriya, Yong Gab Lee, Chang Hee Kang, Kyoung Tae Lee, Yung Hyun Choi, Sung Yong Park, Jae Kwan Hwang, Gi Young Kim

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Piceatannol has potent anti-inflammatory, immunomodulatory, anticancer and antiproliferative effects. However, little is known about the mechanism by which piceatannol inhibits invasion and metastasis. The aim of the current study was to investigate the effects of piceatannol on the expression of matrix metalloproteinase-9 (MMP-9) in DU145 human prostate cancer cells. The results revealed that MMP-9 activity was significantly increased in response to tumor necrosis factor-α (TNF-α). However, treatment with piceatannol reversed TNF-α- and MMP-9-induced gelatin zymography and its gene expression. In addition, a Matrigel invasion assay determined that piceatannol reduces the TNF-α-induced invasion of DU145 cells. Nuclear factor-κ B (NF-κB) is a significant transcription factor that regulates numerous genes involved in tumor cell invasion and metastasis. Therefore, whether piceatannol acts on NF-κB to regulate MMP-9 gene expression was analyzed. The results revealed that piceatannol attenuates MMP-9 gene expression via the suppression of NF-κB activity. Using a specific NF-κB inhibitor, pyrrolidine dithiocarbamate, it was confirmed that TNF-α-induced MMP-9 gene expression is primarily regulated by NF-κB activation. Piceatannol inhibited NF-κB activity by suppressing nuclear translocation of the NF-κB p65 and p50 subunits. Furthermore, TNF-α-induced Akt phosphorylation was significantly downregulated in the presence of piceatannol. The Akt inhibitor LY294002 caused a significant decrease in TNF-α-induced NF-κB activity and MMP-9 gene expression. Overall, these data suggest that piceatannol inhibits TNF-α-induced invasion by suppression of MMP-9 activation via the Akt-mediated NF-κB pathway in DU145 prostate cancer cells.

Original languageEnglish
Pages (from-to)341-347
Number of pages7
JournalOncology Letters
Volume5
Issue number1
DOIs
Publication statusPublished - 2012 Nov 19

Fingerprint

Matrix Metalloproteinase 9
Tumor Necrosis Factor-alpha
Gene Expression
Prostatic Neoplasms
3,3',4,5'-tetrahydroxystilbene
Neoplasm Metastasis
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Gelatin
Anti-Inflammatory Agents
Transcription Factors
Down-Regulation
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Jayasooriya, Rajapaksha Gendara Prasad Tharanga ; Lee, Yong Gab ; Kang, Chang Hee ; Lee, Kyoung Tae ; Choi, Yung Hyun ; Park, Sung Yong ; Hwang, Jae Kwan ; Kim, Gi Young. / Piceatannol inhibits MMP-9-dependent invasion of tumor necrosis factor-α-stimulated DU145 cells by suppressing the Akt-mediated nuclear factor-κB pathway. In: Oncology Letters. 2012 ; Vol. 5, No. 1. pp. 341-347.
@article{40e4e04f15f646d586fd168964fba28e,
title = "Piceatannol inhibits MMP-9-dependent invasion of tumor necrosis factor-α-stimulated DU145 cells by suppressing the Akt-mediated nuclear factor-κB pathway",
abstract = "Piceatannol has potent anti-inflammatory, immunomodulatory, anticancer and antiproliferative effects. However, little is known about the mechanism by which piceatannol inhibits invasion and metastasis. The aim of the current study was to investigate the effects of piceatannol on the expression of matrix metalloproteinase-9 (MMP-9) in DU145 human prostate cancer cells. The results revealed that MMP-9 activity was significantly increased in response to tumor necrosis factor-α (TNF-α). However, treatment with piceatannol reversed TNF-α- and MMP-9-induced gelatin zymography and its gene expression. In addition, a Matrigel invasion assay determined that piceatannol reduces the TNF-α-induced invasion of DU145 cells. Nuclear factor-κ B (NF-κB) is a significant transcription factor that regulates numerous genes involved in tumor cell invasion and metastasis. Therefore, whether piceatannol acts on NF-κB to regulate MMP-9 gene expression was analyzed. The results revealed that piceatannol attenuates MMP-9 gene expression via the suppression of NF-κB activity. Using a specific NF-κB inhibitor, pyrrolidine dithiocarbamate, it was confirmed that TNF-α-induced MMP-9 gene expression is primarily regulated by NF-κB activation. Piceatannol inhibited NF-κB activity by suppressing nuclear translocation of the NF-κB p65 and p50 subunits. Furthermore, TNF-α-induced Akt phosphorylation was significantly downregulated in the presence of piceatannol. The Akt inhibitor LY294002 caused a significant decrease in TNF-α-induced NF-κB activity and MMP-9 gene expression. Overall, these data suggest that piceatannol inhibits TNF-α-induced invasion by suppression of MMP-9 activation via the Akt-mediated NF-κB pathway in DU145 prostate cancer cells.",
author = "Jayasooriya, {Rajapaksha Gendara Prasad Tharanga} and Lee, {Yong Gab} and Kang, {Chang Hee} and Lee, {Kyoung Tae} and Choi, {Yung Hyun} and Park, {Sung Yong} and Hwang, {Jae Kwan} and Kim, {Gi Young}",
year = "2012",
month = "11",
day = "19",
doi = "10.3892/ol.2012.968",
language = "English",
volume = "5",
pages = "341--347",
journal = "Oncology Letters",
issn = "1792-1074",
publisher = "Spandidos Publications",
number = "1",

}

Piceatannol inhibits MMP-9-dependent invasion of tumor necrosis factor-α-stimulated DU145 cells by suppressing the Akt-mediated nuclear factor-κB pathway. / Jayasooriya, Rajapaksha Gendara Prasad Tharanga; Lee, Yong Gab; Kang, Chang Hee; Lee, Kyoung Tae; Choi, Yung Hyun; Park, Sung Yong; Hwang, Jae Kwan; Kim, Gi Young.

In: Oncology Letters, Vol. 5, No. 1, 19.11.2012, p. 341-347.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Piceatannol inhibits MMP-9-dependent invasion of tumor necrosis factor-α-stimulated DU145 cells by suppressing the Akt-mediated nuclear factor-κB pathway

AU - Jayasooriya, Rajapaksha Gendara Prasad Tharanga

AU - Lee, Yong Gab

AU - Kang, Chang Hee

AU - Lee, Kyoung Tae

AU - Choi, Yung Hyun

AU - Park, Sung Yong

AU - Hwang, Jae Kwan

AU - Kim, Gi Young

PY - 2012/11/19

Y1 - 2012/11/19

N2 - Piceatannol has potent anti-inflammatory, immunomodulatory, anticancer and antiproliferative effects. However, little is known about the mechanism by which piceatannol inhibits invasion and metastasis. The aim of the current study was to investigate the effects of piceatannol on the expression of matrix metalloproteinase-9 (MMP-9) in DU145 human prostate cancer cells. The results revealed that MMP-9 activity was significantly increased in response to tumor necrosis factor-α (TNF-α). However, treatment with piceatannol reversed TNF-α- and MMP-9-induced gelatin zymography and its gene expression. In addition, a Matrigel invasion assay determined that piceatannol reduces the TNF-α-induced invasion of DU145 cells. Nuclear factor-κ B (NF-κB) is a significant transcription factor that regulates numerous genes involved in tumor cell invasion and metastasis. Therefore, whether piceatannol acts on NF-κB to regulate MMP-9 gene expression was analyzed. The results revealed that piceatannol attenuates MMP-9 gene expression via the suppression of NF-κB activity. Using a specific NF-κB inhibitor, pyrrolidine dithiocarbamate, it was confirmed that TNF-α-induced MMP-9 gene expression is primarily regulated by NF-κB activation. Piceatannol inhibited NF-κB activity by suppressing nuclear translocation of the NF-κB p65 and p50 subunits. Furthermore, TNF-α-induced Akt phosphorylation was significantly downregulated in the presence of piceatannol. The Akt inhibitor LY294002 caused a significant decrease in TNF-α-induced NF-κB activity and MMP-9 gene expression. Overall, these data suggest that piceatannol inhibits TNF-α-induced invasion by suppression of MMP-9 activation via the Akt-mediated NF-κB pathway in DU145 prostate cancer cells.

AB - Piceatannol has potent anti-inflammatory, immunomodulatory, anticancer and antiproliferative effects. However, little is known about the mechanism by which piceatannol inhibits invasion and metastasis. The aim of the current study was to investigate the effects of piceatannol on the expression of matrix metalloproteinase-9 (MMP-9) in DU145 human prostate cancer cells. The results revealed that MMP-9 activity was significantly increased in response to tumor necrosis factor-α (TNF-α). However, treatment with piceatannol reversed TNF-α- and MMP-9-induced gelatin zymography and its gene expression. In addition, a Matrigel invasion assay determined that piceatannol reduces the TNF-α-induced invasion of DU145 cells. Nuclear factor-κ B (NF-κB) is a significant transcription factor that regulates numerous genes involved in tumor cell invasion and metastasis. Therefore, whether piceatannol acts on NF-κB to regulate MMP-9 gene expression was analyzed. The results revealed that piceatannol attenuates MMP-9 gene expression via the suppression of NF-κB activity. Using a specific NF-κB inhibitor, pyrrolidine dithiocarbamate, it was confirmed that TNF-α-induced MMP-9 gene expression is primarily regulated by NF-κB activation. Piceatannol inhibited NF-κB activity by suppressing nuclear translocation of the NF-κB p65 and p50 subunits. Furthermore, TNF-α-induced Akt phosphorylation was significantly downregulated in the presence of piceatannol. The Akt inhibitor LY294002 caused a significant decrease in TNF-α-induced NF-κB activity and MMP-9 gene expression. Overall, these data suggest that piceatannol inhibits TNF-α-induced invasion by suppression of MMP-9 activation via the Akt-mediated NF-κB pathway in DU145 prostate cancer cells.

UR - http://www.scopus.com/inward/record.url?scp=84869051594&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84869051594&partnerID=8YFLogxK

U2 - 10.3892/ol.2012.968

DO - 10.3892/ol.2012.968

M3 - Article

AN - SCOPUS:84869051594

VL - 5

SP - 341

EP - 347

JO - Oncology Letters

JF - Oncology Letters

SN - 1792-1074

IS - 1

ER -