Pterostilbene, a bioactive component of blueberries, suppresses the generation of breast cancer stem cells within tumor microenvironment and metastasis via modulating NF-κB/microRNA 448 circuit

Ka Kit Mak, Alexander T H Wu, Wei Hwa Lee, Tung Cheng Chang, Jeng Fong Chiou, Liang Shun Wang, Chih Hsiung Wu, Chi Ying F Huang, Yi Shing Shieh, Tsu Yi Chao, Chi Tang Ho, Gow Chin Yen, Chi-Tai Yeh

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Abstract

Scope: Tumor-associated macrophages (TAMs) have been shown to promote metastasis and malignancy. Pterostilbene, a natural stilbene isolated from blueberries, has been suggested for anti-cancer effects. Here, we explored the potential cancer stem cells (CSCs)/TAM modulating effects of pterostilbene in breast cancer. Methods and results: Using flowcytometric and Boyden chamber assay, we showed MCF7 and MDA-MB-231 cells cocultured with M2 TAMs exhibited increased percentage of CD44+/CD24- CSC population and migratory/invasive abilities. RT-PCR results showed that CD44+/CD24- cells expressed an increased level of HIF-1α, β-catenin, Twist1, and NF-κB and enhanced tumor sphere forming ability. Additionally, pterostilbene treatment dose dependently overcame M2 TAM-induced enrichment of CSCs and metastatic potential of breast cancer cells. Mechanistically, pterostilbene suppressed NFκB, Twist1, vimentin, and increased E-cadherin expression. Using siRNA technique, we demonstrated that pterostilbene-mediated NFκB downregulation was correlated to an increased amount of microRNA 448. Finally, pterostilbene-mediated suppression in tumorigenesis and metastasis was validated by noninvasive bioluminescence in mice bearing M2 TAM cocultured MDA-MB-231 tumor.

Original languageEnglish
Pages (from-to)1123-1134
Number of pages12
JournalMolecular Nutrition and Food Research
Volume57
Issue number7
DOIs
Publication statusPublished - Jul 2013

Fingerprint

Blueberry Plants
Tumor Microenvironment
Neoplastic Stem Cells
blueberries
MicroRNAs
microRNA
metastasis
breast neoplasms
stem cells
Breast Neoplasms
Neoplasm Metastasis
neoplasms
macrophages
Neoplasms
Macrophages
stilbenes
bioluminescence
cadherins
vimentin
small interfering RNA

Keywords

  • Breast cancer stem cells
  • Epithelial-to-mesenchymal transition
  • MiR448
  • Pterostilbene
  • Tumor-associated macrophages

ASJC Scopus subject areas

  • Food Science
  • Biotechnology

Cite this

@article{24440680f0e24aabb602ca155578a337,
title = "Pterostilbene, a bioactive component of blueberries, suppresses the generation of breast cancer stem cells within tumor microenvironment and metastasis via modulating NF-κB/microRNA 448 circuit",
abstract = "Scope: Tumor-associated macrophages (TAMs) have been shown to promote metastasis and malignancy. Pterostilbene, a natural stilbene isolated from blueberries, has been suggested for anti-cancer effects. Here, we explored the potential cancer stem cells (CSCs)/TAM modulating effects of pterostilbene in breast cancer. Methods and results: Using flowcytometric and Boyden chamber assay, we showed MCF7 and MDA-MB-231 cells cocultured with M2 TAMs exhibited increased percentage of CD44+/CD24- CSC population and migratory/invasive abilities. RT-PCR results showed that CD44+/CD24- cells expressed an increased level of HIF-1α, β-catenin, Twist1, and NF-κB and enhanced tumor sphere forming ability. Additionally, pterostilbene treatment dose dependently overcame M2 TAM-induced enrichment of CSCs and metastatic potential of breast cancer cells. Mechanistically, pterostilbene suppressed NFκB, Twist1, vimentin, and increased E-cadherin expression. Using siRNA technique, we demonstrated that pterostilbene-mediated NFκB downregulation was correlated to an increased amount of microRNA 448. Finally, pterostilbene-mediated suppression in tumorigenesis and metastasis was validated by noninvasive bioluminescence in mice bearing M2 TAM cocultured MDA-MB-231 tumor.",
keywords = "Breast cancer stem cells, Epithelial-to-mesenchymal transition, MiR448, Pterostilbene, Tumor-associated macrophages",
author = "Mak, {Ka Kit} and Wu, {Alexander T H} and Lee, {Wei Hwa} and Chang, {Tung Cheng} and Chiou, {Jeng Fong} and Wang, {Liang Shun} and Wu, {Chih Hsiung} and Huang, {Chi Ying F} and Shieh, {Yi Shing} and Chao, {Tsu Yi} and Ho, {Chi Tang} and Yen, {Gow Chin} and Chi-Tai Yeh",
year = "2013",
month = "7",
doi = "10.1002/mnfr.201200549",
language = "English",
volume = "57",
pages = "1123--1134",
journal = "Molecular Nutrition and Food Research",
issn = "1613-4125",
publisher = "Wiley-VCH Verlag",
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TY - JOUR

T1 - Pterostilbene, a bioactive component of blueberries, suppresses the generation of breast cancer stem cells within tumor microenvironment and metastasis via modulating NF-κB/microRNA 448 circuit

AU - Mak, Ka Kit

AU - Wu, Alexander T H

AU - Lee, Wei Hwa

AU - Chang, Tung Cheng

AU - Chiou, Jeng Fong

AU - Wang, Liang Shun

AU - Wu, Chih Hsiung

AU - Huang, Chi Ying F

AU - Shieh, Yi Shing

AU - Chao, Tsu Yi

AU - Ho, Chi Tang

AU - Yen, Gow Chin

AU - Yeh, Chi-Tai

PY - 2013/7

Y1 - 2013/7

N2 - Scope: Tumor-associated macrophages (TAMs) have been shown to promote metastasis and malignancy. Pterostilbene, a natural stilbene isolated from blueberries, has been suggested for anti-cancer effects. Here, we explored the potential cancer stem cells (CSCs)/TAM modulating effects of pterostilbene in breast cancer. Methods and results: Using flowcytometric and Boyden chamber assay, we showed MCF7 and MDA-MB-231 cells cocultured with M2 TAMs exhibited increased percentage of CD44+/CD24- CSC population and migratory/invasive abilities. RT-PCR results showed that CD44+/CD24- cells expressed an increased level of HIF-1α, β-catenin, Twist1, and NF-κB and enhanced tumor sphere forming ability. Additionally, pterostilbene treatment dose dependently overcame M2 TAM-induced enrichment of CSCs and metastatic potential of breast cancer cells. Mechanistically, pterostilbene suppressed NFκB, Twist1, vimentin, and increased E-cadherin expression. Using siRNA technique, we demonstrated that pterostilbene-mediated NFκB downregulation was correlated to an increased amount of microRNA 448. Finally, pterostilbene-mediated suppression in tumorigenesis and metastasis was validated by noninvasive bioluminescence in mice bearing M2 TAM cocultured MDA-MB-231 tumor.

AB - Scope: Tumor-associated macrophages (TAMs) have been shown to promote metastasis and malignancy. Pterostilbene, a natural stilbene isolated from blueberries, has been suggested for anti-cancer effects. Here, we explored the potential cancer stem cells (CSCs)/TAM modulating effects of pterostilbene in breast cancer. Methods and results: Using flowcytometric and Boyden chamber assay, we showed MCF7 and MDA-MB-231 cells cocultured with M2 TAMs exhibited increased percentage of CD44+/CD24- CSC population and migratory/invasive abilities. RT-PCR results showed that CD44+/CD24- cells expressed an increased level of HIF-1α, β-catenin, Twist1, and NF-κB and enhanced tumor sphere forming ability. Additionally, pterostilbene treatment dose dependently overcame M2 TAM-induced enrichment of CSCs and metastatic potential of breast cancer cells. Mechanistically, pterostilbene suppressed NFκB, Twist1, vimentin, and increased E-cadherin expression. Using siRNA technique, we demonstrated that pterostilbene-mediated NFκB downregulation was correlated to an increased amount of microRNA 448. Finally, pterostilbene-mediated suppression in tumorigenesis and metastasis was validated by noninvasive bioluminescence in mice bearing M2 TAM cocultured MDA-MB-231 tumor.

KW - Breast cancer stem cells

KW - Epithelial-to-mesenchymal transition

KW - MiR448

KW - Pterostilbene

KW - Tumor-associated macrophages

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JO - Molecular Nutrition and Food Research

JF - Molecular Nutrition and Food Research

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