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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, Canada.
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.
Insights
Polyphenol-enriched blueberry preparation (PEBP) effectively inhibited skin cancer stem cell proliferation and reduced metastasis. PEBP also upregulated tumor-suppressing microRNAs, demonstrating its potential as a natural skin cancer chemopreventive agent.
Area of Science:
- * Dermatology and Oncology
- * Natural Product Chemistry
- * Epigenetics and Molecular Biology
Background:
- * Solar UV radiation exposure is a primary cause of skin cancer, inducing DNA damage and cellular pathway dysregulation.
- * Photochemoprevention using natural products, particularly polyphenols, offers a promising strategy for controlling skin cancer.
- * Polyphenols can inhibit cancer stem cells (CSCs) and modulate microRNA expression, impacting cancer progression.
Purpose of the Study:
- * To evaluate the effects of polyphenol-enriched blueberry preparation (PEBP) and non-fermented blueberry juice (NBJ) on microRNA expression and target proteins in skin cancer.
- * To assess the impact of PEBP and NBJ on skin CSC stemness, motility, and invasiveness.
Main Methods:
- * Treatment of melanoma cell lines (HS 294T and B16F10) with PEBP and NBJ.
- * Analysis of skin CSC proliferation, melanophore formation, and CD133+ stem cell marker expression.
- * Quantification of microRNA (miR-200s) and target protein (ZEB1) expression levels.
Main Results:
- * PEBP significantly inhibited the proliferation of skin CSCs and reduced melanophore formation in melanoma cell lines.
- * PEBP treatment led to a significant decrease in CD133+ stem cell marker expression compared to NBJ and control groups.
- * PEBP upregulated tumor suppressors miR-200s and modulated their target protein ZEB1, indicating anti-metastatic effects.
Conclusions:
- * PEBP exhibits significant anticancer and anti-metastatic properties against skin cancer.
- * The study highlights PEBP's potential as a novel chemopreventive agent for skin cancer.
- * Modulation of microRNA expression and CSC markers by PEBP provides mechanistic insights into its therapeutic effects.
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