Role of a Polyphenol-Enriched Blueberry Preparation on Inhibition of Melanoma Cancer Stem Cells and Modulation of MicroRNAs

Author:

Alsadi Nawal1,Yahfoufi Nour1,Nessim Carolyn2ORCID,Matar Chantal13

Affiliation:

1. Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada

2. Department of Surgery, University of Ottawa, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada

3. School of Nutrition Sciences, Faculty of Health Sciences, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada

Abstract

Melanoma is a type of skin cancer known for its high mortality rate. Cancer stem cells (CSCs) are a subpopulation of cancer cells that significantly contribute to tumour recurrence and differentiation. Epigenetic-specific changes involving miRNAs maintain CSCs. Plant polyphenols have been reported to be involved in cancer chemoprevention and chemotherapy, with miRNAs being the novel effectors in their biological activities. A polyphenol-enriched blueberry preparation (PEBP) derived from fermented blueberries has demonstrated promising chemopreventative properties on breast cancer stem cells by influencing inflammatory pathways and miRNAs. In our current investigation, we seek to unveil the impact of PEBP on inhibiting melanoma development and to elucidate the underlying mechanisms. Our study employs various human cell lines, including an ex vivo cell line derived from a patient’s metastatic tumour. We found that it elevates miR-200c, increasing E-cadherin expression and inhibiting miR-210-3p through NF-κB signalling, impacting Epithelial-to-Mesenchymal Transition (EMT), a critical process in cancer progression. PEBP increases the SOCS1 expression, potentially contributing to miR-210-3p inhibition. Experiments involving miRNA manipulation confirm their functional roles. The study suggests that PEBP’s anti-inflammatory effects involve regulating miR-200c and miR-210 expression and their targets in EMT-related pathways. The overall aim is to provide evidence-based supportive care and preclinical evaluation of PEBP, offering a promising strategy for skin cancer chemoprevention.

Funder

Saudi Arabian Cultural Bureau in Canada

Publisher

MDPI AG

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