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Triterpene Acid (3-O-p-Coumaroyltormentic Acid) Isolated From Aronia Extracts Inhibits Breast Cancer Stem Cell Formation through Downregulation of c-Myc Protein

1
Department of Biotechnology, College of Applied Life Science, Jeju National University, Jeju 63243, Korea
2
Subtropical/tropical organism gene bank, Jeju National University, Jeju 63243, Korea
3
Aroma Biotechnology Center, Jeju National University, Jeju 63243, Korea
4
Division of Biotechnology, College of Environmental and Bioresource Sciences, Chonbuk National University, Gobong-ro 79, Iksan 54596, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2018, 19(9), 2528; https://doi.org/10.3390/ijms19092528
Received: 23 July 2018 / Revised: 23 August 2018 / Accepted: 24 August 2018 / Published: 26 August 2018
(This article belongs to the Section Bioactives and Nutraceuticals)
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Abstract

Cancer stem cells (CSCs) are drug-resistant and radiation-resistant cancer cells that are responsible for tumor progression and maintenance, cancer recurrence, and metastasis. Targeting breast CSCs with phytochemicals is a new paradigm for cancer prevention and treatment. In this study, activity-guided fractionation from mammosphere formation inhibition assays, repeated chromatographic preparations over silica gel, preparatory thin layer chromatography, and HPLC using aronia extracts led to the isolation of one compound. Using 1H and 13C 2-dimensional nuclear magnetic resonance (NMR) as well as electrospray ionization (ESI) mass spectrometry, the isolated compound was identified as 3-O-p-coumaroyltormentic acid. This compound inhibits breast cancer cell proliferation and mammosphere formation in a dose-dependent manner and reduces the CD44high/CD24low subpopulation and aldehyde dehydrogenase (ALDH)-expressing cell population as well as the expression of the self-renewal-related genes CD44, SOX2, and OCT4. 3-O-p-Coumaroyltormentic acid preferentially reduced the protein levels of c-Myc, which is a CSC survival factor, by inducing c-Myc degradation. These findings indicate the novel utilization of 3-O-p-coumaroyltormentic acid for breast cancer therapy via disruption of c-Myc protein, which is a CSC survival factor. View Full-Text
Keywords: breast cancer stem cells (CSCs); 3-O-p-coumaroyltormentic acid; mammospheres; c-Myc breast cancer stem cells (CSCs); 3-O-p-coumaroyltormentic acid; mammospheres; c-Myc
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Choi, H.S.; Kim, S.-L.; Kim, J.-H.; Deng, H.-Y.; Yun, B.-S.; Lee, D.-S. Triterpene Acid (3-O-p-Coumaroyltormentic Acid) Isolated From Aronia Extracts Inhibits Breast Cancer Stem Cell Formation through Downregulation of c-Myc Protein. Int. J. Mol. Sci. 2018, 19, 2528.

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