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

Research output: Contribution to journalArticle

56 Citations (Scopus)

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

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Keywords

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

ASJC Scopus subject areas

  • Food Science
  • Biotechnology

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