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
Mak KK, Wu AT, Lee WH, Chang TC, Chiou JF, Wang LS, Wu CH, Huang CY, Shieh YS, Chao TY, Ho CT, Yen GC, Yeh CT
Molecular nutrition & food research · 82 citations
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- People, plus animal or lab work
- Main outcome
- Clinical events such as disease or death
Who paid for it
- Funding
- Independent funding
- Government
- Ministry of Education, Taiwan
- Government
- NSC
- University or hospital
- Center of Excellence for Cancer Research at Taipei Medical University
Based on 3 listed funder(s).
Publication
- Published
- 2013-03-15 · Mol Nutr Food Res · vol. 57 · issue 7 · pp. 1123–1134
- Publisher
- Wiley
- Cited
- 112 citations · more than 93% of similar papers · 3.9× the field average
- Impact
- Top 10% most cited in its field
- References
- 35 works
- Access
- Paywalled
- Research areas
- Sirtuins and Resveratrol in Medicine · Cancer Cells and Metastasis · Immune cells in cancer
- Keywords
- Pterostilbene, Cancer research, Metastasis, Carcinogenesis, Cancer stem cell, Cancer, Downregulation and upregulation, Chemistry, microRNA, NF-κB, Tumor microenvironment, Breast cancer, Biology, Pharmacology, Signal transduction, Medicine, Resveratrol, Internal medicine, Biochemistry, Tumor cells
- MeSH
- cell line, tumor, animals, humans, mice, mice, scid, breast neoplasms, stilbenes, vimentin, nf-kappa b, cadherins, nuclear proteins, micrornas, antigens, cd, down-regulation, gene silencing, female, beta catenin, hypoxia-inducible factor 1, alpha subunit, neoplastic stem cells, epithelial-mesenchymal transition, tumor microenvironment, mcf-7 cells, carcinogenesis, blueberry plants, twist-related protein 1, hyaluronan receptors
13 authors
From TW, US
- Ka‐Kit MakTaipei Medical University
- Alexander T.H. WuTaipei Medical University Hospital; Taipei Medical University
- Wei‐Hwa LeeTaipei Medical University-Shuang Ho Hospital
- Tung‐Cheng ChangTaipei Medical University-Shuang Ho Hospital; Taipei Medical University
- Jeng‐Fong ChiouTaipei Medical University Hospital; Taipei Medical University
- L.S. WangTaipei Medical University-Shuang Ho Hospital; Taipei Medical University
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.
Conclusion
Pterostilbene effectively suppresses the generation of CSCs and metastatic potential under the influence of M2 TAMs via modulating EMT associated signaling pathways, specifically NF-κB/miR488 circuit. Thus, pterostilbene could be an ideal anti-CSC agent in clinical settings.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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