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Estudio2013

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 citas

Cómo se estudió

Diseño
Estudio in vitro o de mecanismos (clasificado por nuestro filtro de IA)
Estudiado en
Personas, más trabajo en animales o laboratorio
Resultado principal
Eventos clínicos como enfermedad o muerte

Quién lo pagó

Financiación
Financiación independiente
Gobierno
Ministry of Education, Taiwan
Gobierno
NSC
Universidad u hospital
Center of Excellence for Cancer Research at Taipei Medical University

Según 3 financiadores declarados.

Publicación

Publicado
2013-03-15 · Mol Nutr Food Res · vol. 57 · número 7 · págs. 1123–1134
Editorial
Wiley
Citado
112 citas · más que el 93% de estudios similares · 3.9× el promedio de su campo
Impacto
Entre el 10 % más citado de su campo
Referencias
35 trabajos
Acceso
De pago
Áreas de investigación
Sirtuins and Resveratrol in Medicine · Cancer Cells and Metastasis · Immune cells in cancer
Palabras clave
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 autores

  • Ka‐Kit Mak🇹🇼Taipei Medical University
  • Alexander T.H. Wu🇹🇼Taipei Medical University Hospital; Taipei Medical University
  • Wei‐Hwa Lee🇹🇼Taipei Medical University-Shuang Ho Hospital
  • Tung‐Cheng Chang🇹🇼Taipei Medical University-Shuang Ho Hospital; Taipei Medical University
  • Jeng‐Fong Chiou🇹🇼Taipei Medical University Hospital; Taipei Medical University
  • L.S. Wang🇹🇼Taipei Medical University-Shuang Ho Hospital; Taipei Medical University
  • Chih‐Hsiung Wu🇹🇼Taipei Medical University-Shuang Ho Hospital
  • Chi‐Ying F. Huang🇹🇼National Yang Ming Chiao Tung University; National Yang Ming University Hospital; National Yang Ming Chiao Tung University
  • Yi‐Shing Shieh🇹🇼Tri-Service General Hospital; National Defense Medical Center
  • Tsu‐Yi Chao🇹🇼Taipei Medical University-Shuang Ho Hospital; Taipei Medical University
  • Chi‐Tang Ho🇺🇸Rutgers, The State University of New Jersey
  • Gow‐Chin Yen🇹🇼 · autor de correspondenciaNational Chung Hsing University
  • Chi‐Tai Yeh🇹🇼 · autor de correspondenciaTaipei Medical University-Shuang Ho Hospital; Taipei Medical University; National Defense Medical Center

Resumen

El texto original del estudio, en el idioma en que se publicó.

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.

Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial.

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