Invadopodia-associated proteins blockade as a novel mechanism for 6-shogaol and pterostilbene to reduce breast cancer cell motility and invasion

Bo Han Hong, Chi Hao Wu, Chi-Tai Yeh, Gow Chin Yen

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Scope: Invadopodia are actin-rich membrane protrusions of tumor cells that are thought to initiate the local migration and invasion during cancer metastasis. The blockade of invadopodia-associated proteins has been reported as a promising approach for prevention of tumor metastasis. The aim of this study was to investigate the modulatory effects of 6-shogaol and pterostilbene on invadopodia in aggressive breast cancer cells. Methods and results: By wound-healing, transwell, and gelatin zymography assays, we found that 6-shogaol and pterostilbene effectively attenuated the motility and invasion of MDA-MB-231 cells, and suppressed the activities of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). Further investigation into the underlying molecular mechanisms revealed that the levels of key modulators of invadopodium maturation, including c-Src kinase, cortactin, and membrane type 1-matrix metalloproteinase (MT1-MMP) decreased when cells were treated with 6-shogaol or pterostilbene. Conclusion: These data suggest that the repression of these factors might affect the maturation of invadopodia, inhibiting the metastasis of MDA-MB-231 cells. In conclusion, the present study demonstrates for the first time that 6-shogaol and pterostilbene can inhibit invadopodium formation and MMP activity in highly invasive breast cancer cells. We suggest that these compounds may be clinically useful in chemopreventive treatments for metastatic breast cancer.

Original languageEnglish
Pages (from-to)886-895
Number of pages10
JournalMolecular Nutrition and Food Research
Volume57
Issue number5
DOIs
Publication statusPublished - May 2013

Fingerprint

cell invasion
cell movement
breast neoplasms
Cell Movement
metastasis
Breast Neoplasms
Proteins
proteins
Neoplasm Metastasis
interstitial collagenase
gelatinase A
gelatinase B
neoplasms
cells
Cell Surface Extensions
Cortactin
tissue repair
gelatin
Matrix Metalloproteinase 14
actin

Keywords

  • 6-Shogaol
  • Breast cancer
  • Invadopodia
  • Metastasis
  • Pterostilbene

ASJC Scopus subject areas

  • Food Science
  • Biotechnology

Cite this

Invadopodia-associated proteins blockade as a novel mechanism for 6-shogaol and pterostilbene to reduce breast cancer cell motility and invasion. / Hong, Bo Han; Wu, Chi Hao; Yeh, Chi-Tai; Yen, Gow Chin.

In: Molecular Nutrition and Food Research, Vol. 57, No. 5, 05.2013, p. 886-895.

Research output: Contribution to journalArticle

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AB - Scope: Invadopodia are actin-rich membrane protrusions of tumor cells that are thought to initiate the local migration and invasion during cancer metastasis. The blockade of invadopodia-associated proteins has been reported as a promising approach for prevention of tumor metastasis. The aim of this study was to investigate the modulatory effects of 6-shogaol and pterostilbene on invadopodia in aggressive breast cancer cells. Methods and results: By wound-healing, transwell, and gelatin zymography assays, we found that 6-shogaol and pterostilbene effectively attenuated the motility and invasion of MDA-MB-231 cells, and suppressed the activities of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). Further investigation into the underlying molecular mechanisms revealed that the levels of key modulators of invadopodium maturation, including c-Src kinase, cortactin, and membrane type 1-matrix metalloproteinase (MT1-MMP) decreased when cells were treated with 6-shogaol or pterostilbene. Conclusion: These data suggest that the repression of these factors might affect the maturation of invadopodia, inhibiting the metastasis of MDA-MB-231 cells. In conclusion, the present study demonstrates for the first time that 6-shogaol and pterostilbene can inhibit invadopodium formation and MMP activity in highly invasive breast cancer cells. We suggest that these compounds may be clinically useful in chemopreventive treatments for metastatic breast cancer.

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