Role of a polyphenol-enriched preparation on chemoprevention of mammary carcinoma through cancer stem cells and inflammatory pathways modulation

Journal of Translational Medicine

Research

Maria Ouzounova¹  Jean-François Mallet²  Zdenko Herceg³  Hector Hernandez-Vargas³  Chantal Matar⁴  Sam Rahbar⁴  Tri Vuong⁴ 

[1]Cancer Center, Georgia Regents University, Augusta, GA, USA

[2]Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Canada

[3]International Agency for Research on Cancer, Lyon, France

[4]Nutritional Sciences Program, Faculty of Health Sciences, University of Ottawa, R2057 Roger Guindon Hall, 451 Smyth Road, K1H 8M5, Ottawa, ON, Canada

关键词: Polyphenols;    Breast cancer stem cells;    Tumor;    Metastasis;    STAT3;    MAPKs;   

DOI  :  10.1186/s12967-016-0770-7

 received in 2015-10-23, accepted in 2015-12-21,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundNaturally occurring polyphenolic compounds from fruits, particularly from blueberries, have been reported to be significantly involved in cancer chemoprevention and chemotherapy. Biotransformation of blueberry juice by Serratia vaccinii increases its polyphenolic content and endows it with anti-inflammatory properties.MethodsThis study evaluated the effect of a polyphenol-enriched blueberry preparation (PEBP) and its non-fermented counterpart (NBJ), on mammary cancer stem cell (CSC) development in in vitro, in vivo and ex vivo settings. Effects of PEBP on cell proliferation, mobility, invasion, and mammosphere formation were measured in vitro in three cell lines: murine 4T1 and human MCF7 and MDA-MB-231. Ex vivo mammosphere formation, tumor growth and metastasis observations were carried out in a BALB/c mouse model.ResultsOur research revealed that PEBP influence cellular signaling cascades of breast CSCs, regulating the activity of transcription factors and, consequently, inhibiting tumor growth in vivo by decreasing metastasis and controlling PI3K/AKT, MAPK/ERK, and STAT3 pathways, central nodes in CSC inflammatory signaling. PEBP significantly inhibited cell proliferation of 4T1, MCF-7 and MDA-MB-231. In all cell lines, PEBP reduced mammosphere formation, cell mobility and cell migration. In vivo, PEBP significantly reduced tumor development, inhibited the formation of ex vivo mammospheres, and significantly reduced lung metastasis.ConclusionsThis study showed that polyphenol enrichment of a blueberry preparation by fermentation increases its chemopreventive potential by protecting mice against tumor development, inhibiting the formation of cancer stem cells and reducing lung metastasis. Thus, PEBP may represent a novel complementary alternative medicine therapy and a source for novel therapeutic agents against breast cancer.

【 授权许可】

CC BY   
© Vuong et al. 2016