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Journal of Cancer Prevention

Original Article

J Cancer Prev 2021; 26(3): 162-173

Published online September 30, 2021

https://doi.org/10.15430/JCP.2021.26.3.162

© Korean Society of Cancer Prevention

miRNA-200b Signature in the Prevention of Skin Cancer Stem Cells by Polyphenol-enriched Blueberry Preparation

Nawal Alsadi1 , Jean-François Mallet1 , Chantal Matar1,2

1Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 2Department of Nutrition Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, Canada

Correspondence to :
Chantal Matar, E-mail: Chantal.matar@uottawa.ca, https://orcid.org/0000-0003-0346-4751

Received: June 24, 2021; Revised: September 18, 2021; Accepted: September 23, 2021

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Exposure of the skin to solar UV radiation leads to inflammation, DNA damage, and dysregulation of cellular signaling pathways, which may cause skin cancer. Photochemoprevention with natural products is an effective strategy for the control of cutaneous neoplasia. Polyphenols have been proven to help prevent skin cancer and to inhibit the growth of cancer stem cells (CSCs) through epigenetic mechanisms, including modulation of microRNAs expression. Thus, the current study aimed to assess the effect of polyphenol enriched blueberry preparation (PEBP) or non-fermented blueberry juice (NBJ) on expression of miRNAs and target proteins associated with different clinicopathological characteristics of skin cancer such as stemness, motility, and invasiveness. We observed that PEBP significantly inhibited the proliferation of skin CSCs derived from different melanoma cell lines, HS 294T and B16F10. Moreover, PEBP was able to reduce the formation of melanophores. We also showed that the expression of the CD133+ stem cell marker in B16F10 and HS294T cell lines was significantly decreased after treating the cells with PEBP in comparison to the NBJ and control groups. Importantly, tumor suppressors’ miR-200s, involved in the regulation of the epithelial-to-mesenchymal transition and metastasis, were strikingly upregulated. In addition, we have shown that a protein target of the tumor suppressor miR200b, ZEB1, was also significantly modulated. Thus, the results demonstrates that PEBP possesses potent anticancer and anti-metastatic potentials and may represent a novel chemopreventative agent against skin cancer.

Keywords: Polyphenols, Cancer stem cells, Neoplasm metastasis, MicroRNA-200b, Zinc finger E-box binding homeobox 1

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