scholarly journals Polyphenol-Enriched Blueberry Preparation Controls Breast Cancer Stem Cells by Targeting FOXO1 and miR-145

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4330
Author(s):  
Jean-François Mallet ◽  
Roghayeh Shahbazi ◽  
Nawal Alsadi ◽  
Chantal Matar

Scientific evidence supports the early deregulation of epigenetic profiles during breast carcinogenesis. Research shows that cellular transformation, carcinogenesis, and stemness maintenance are regulated by epigenetic-specific changes that involve microRNAs (miRNAs). Dietary bioactive compounds such as blueberry polyphenols may modulate susceptibility to breast cancer by the modulation of CSC survival and self-renewal pathways through the epigenetic mechanism, including the regulation of miRNA expression. Therefore, the current study aimed to assay the effect of polyphenol enriched blueberry preparation (PEBP) or non-fermented blueberry juice (NBJ) on the modulation of miRNA signature and the target proteins associated with different clinical-pathological characteristics of breast cancer such as stemness, invasion, and chemoresistance using breast cancer cell lines. To this end, 4T1 and MB-MDM-231 cell lines were exposed to NBJ or PEBP for 24 h. miRNA profiling was performed in breast cancer cell cultures, and RT-qPCR was undertaken to assay the expression of target miRNA. The expression of target proteins was examined by Western blotting. Profiling of miRNA revealed that several miRNAs associated with different clinical-pathological characteristics were differentially expressed in cells treated with PEBP. The validation study showed significant downregulation of oncogenic miR-210 expression in both 4T1 and MDA-MB-231 cells exposed to PEBP. In addition, expression of tumor suppressor miR-145 was significantly increased in both cell lines treated with PEBP. Western blot analysis showed a significant increase in the relative expression of FOXO1 in 4T1 and MDA-MB-231 cells exposed to PEBP and in MDA-MB-231 cells exposed to NBJ. Furthermore, a significant decrease was observed in the relative expression of N-RAS in 4T1 and MDA-MB-231 cells exposed to PEBP and in MDA-MB-231 cells exposed to NBJ. Our data indicate a potential chemoprevention role of PEBP through the modulation of miRNA expression, particularly miR-210 and miR-145, and protection against breast cancer development and progression. Thus, PEBP may represent a source for novel chemopreventative agents against breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e12019-e12019
Author(s):  
Eduardo Tormo ◽  
Begoña Pineda ◽  
Sandra Ballester ◽  
Octavio Burgues ◽  
Eva Serna ◽  
...  

e12019 Background: Mature microRNAs (miRNAs) are a class of naturally occurring, small non-coding RNA molecules, about 21–25 nucleotides. Growing evidence shows that miRNAs exhibit a variety of regulatory functions related to cell growth, development, and differentiation, and are associated with a wide variety of human diseases. Several miRNAs have been linked to cancer; since expression analysis studies have revealed perturbed miRNA expression in tumors compared to normal tissues. As a consequence, human miRNAs are likely to be highly useful as biomarkers, especially for future cancer diagnostics, and are emerging as targets for disease intervention. Since doxorubicin (DOX) has been used for a long time in breast cancer treatment, and resistance mechanisms are not clear understood, the aim of this work was to find a miRNA expression profile that could explain the regulation in different breast cancer cell lines under DOX treatment. Methods: Three breast cancer cell lines (MDA-MB-231, MDA-MB-468, and MCF-7) were cultured in normal conditions and also treated with DOX. Total RNA containing small non-coding RNA was isolated and its expression profile was performed by using GeneChip miRNA 2.0 array. Real time PCR validation was carried out to confirm the results. Results: Principal Component Analysis (PCA) of the small non-coding RNA profiles showed different expression patterns between normal conditions and DOX treatment in each cell line separately. Taken together in a Heat Map, miRNA expression profiles of MDA-MB-231 and MDA-MB-468 cell lines were closer in both normal and DOX treatment conditions, while miRNA expression profile of MCF-7 cell line showed strong differences. Total of 13 common miRNAs between the three cell lines were found to be significantly affected by DOX treatment. PCR validation confirmed the results obtained. Conclusions: We conclude that 13 common miRNAs are responsables of changes compared to treatment with DOX in breast cancer cell lines MDA-MB-231, MDA-MB-468 and MCF-7. This miRNAs are mainly related with cellular processes such as cell differentiation, vascularisation, apoptosis and cell proliferation and also involved in other cellular processes, such as cell migration.


2018 ◽  
Vol 8 (3) ◽  
pp. 159 ◽  
Author(s):  
Meghan Fragis ◽  
Abdulmonem I. Murayyan ◽  
Suresh Neethirajan

Background: Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer deaths among Canadian women. Cancer management through changes in lifestyle, such as increased intake of foods rich in dietary flavonoids, have been shown to decrease the risk associated with breast, liver, colorectal, and upper-digestive cancers in epidemiologic studies. Onions are high in flavonoid content and one of the most common vegetables. Additionally, onions are used in most Canadian cuisines.Methods: We investigated the effect of five prominent Ontario grown onion (Stanley, Ruby Ring, LaSalle, Fortress, and Safrane) extracts on two subtypes of breast cancer cell lines: a triple negative breast cancer line MDA-MB-231 and an ER+ breast cancer line MCF-7.Results: These onion extracts elicited strong anti-proliferative, anti-migratory, and cytotoxic activities on both the cancer cell lines. Flavonoids present in these onion extracts induced apoptosis, cell cycle arrest in the G2/M phase, and a reduction in mitochondrial membrane potential at dose-dependent concentrations. Onion extracts were more effective against MDA-MB-231 compared to the MCF-7 cell line. Conclusion: In this study, we investigated the extracts synthesized from Ontario-grown onion varieties in inducing anti-migratory, cytostatic, and cytotoxic activities in two sub-types of human breast cancer cell lines. Anti-tumor activity of these extracts depends upon the varietal and can be formulated into nutraceuticals and functional foods for the wellbeing of cancer patients. Overall, the results suggest that onion extracts are a good source of flavonoids with anti-cancerous properties.Keywords: onion extracts; flavonoids; anti-proliferative; breast cancer; cytotoxic activity


2017 ◽  
Vol 63 (1) ◽  
pp. 141-145
Author(s):  
Yuliya Khochenkova ◽  
Eliso Solomko ◽  
Oksana Ryabaya ◽  
Yevgeniya Stepanova ◽  
Dmitriy Khochenkov

The discovery for effective combinations of anticancer drugs for treatment for breast cancer is the actual problem in the experimental chemotherapy. In this paper we conducted a study of antitumor effect of the combination of sunitinib and bortezomib against MDA-MB-231 and SKBR-3 breast cancer cell lines in vitro. We found that bortezomib in non-toxic concentrations can potentiate the antitumor activity of sunitinib. MDA-MB-231 cell line has showed great sensitivity to the combination of bortezomib and sunitinib in vitro. Bortezomib and sunitinib caused reduced expression of receptor tyrosine kinases VEGFR1, VEGFR2, PDGFRa, PDGFRß and c-Kit on HER2- and HER2+ breast cancer cell lines


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