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.
Highlights
Aronia (Aronia melanocarpa) berries, known as black chokeberries, have recently gained great popularity among consumers primarily owing to their high health benefits [1]
We demonstrate that 3-O-p-coumaroyltormentic acid exerts anti-Cancer stem cells (CSCs) activity against breast cancer through the deregulation of c-Myc expression, which is a CSC survival factor
We concluded that the methanol extracts contained the CSC inhibitor (Figure 1A)
Summary
Aronia (Aronia melanocarpa) berries, known as black chokeberries, have recently gained great popularity among consumers primarily owing to their high health benefits [1]. Cancer stem cells (CSCs) were first identified in myeloid leukemia [9], and later were reported as a subpopulation of various solid tumors, including breast, brain, colon, ovarian, pancreatic, and prostate cancer [10]. Much evidence has shown that many types of cancer (including breast cancer) originate from CSCs, which compose a small population within the tumor [11]. This subpopulation produces the tumor bulk through self-renewal and differentiation [12]. We demonstrate that 3-O-p-coumaroyltormentic acid exerts anti-CSC activity against breast cancer through the deregulation of c-Myc expression, which is a CSC survival factor
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