In:
Molecular Nutrition & Food Research, Wiley, Vol. 57, No. 7 ( 2013-07), p. 1123-1134
Abstract:
Tumor‐associated macrophages ( TAM s) 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 ( CSC s)/ TAM modulating effects of pterostilbene in breast cancer. Methods and results Using flowcytometric and B oyden chamber assay, we showed MCF 7 and MDA ‐ MB ‐231 cells cocultured with M 2 TAM s exhibited increased percentage of CD 44 + / CD 24 − CSC population and migratory/invasive abilities. RT ‐ PCR results showed that CD 44 + / CD 24 − cells expressed an increased level of HIF ‐1α, β‐catenin, T wist1, and NF ‐κB and enhanced tumor sphere forming ability. Additionally, pterostilbene treatment dose dependently overcame M 2 TAM ‐induced enrichment of CSC s and metastatic potential of breast cancer cells. Mechanistically, pterostilbene suppressed NF κ B , T wist1, vimentin, and increased E ‐cadherin expression. Using si RNA technique, we demonstrated that pterostilbene‐mediated NF κ B 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 M 2 TAM cocultured MDA ‐ MB ‐231 tumor. Conclusion Pterostilbene effectively suppresses the generation of CSC s and metastatic potential under the influence of M 2 TAM s via modulating EMT associated signaling pathways, specifically NF ‐κ B /mi R 488 circuit. Thus, pterostilbene could be an ideal anti‐ CSC agent in clinical settings.
Type of Medium:
Online Resource
ISSN:
1613-4125
,
1613-4133
DOI:
10.1002/mnfr.201200549
Language:
English
Publisher:
Wiley
Publication Date:
2013
detail.hit.zdb_id:
2160372-8
SSG:
12
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