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 Aug 26;19(9):2528. doi: 10.3390/ijms19092528.


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.

Keywords: 3-O-p-coumaroyltormentic acid; breast cancer stem cells (CSCs); c-Myc; mammospheres.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Biomarkers
  • Biomarkers, Tumor
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • CD24 Antigen / metabolism
  • Cell Proliferation / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Hyaluronan Receptors / metabolism
  • Molecular Structure
  • Neoplastic Stem Cells / metabolism*
  • Proto-Oncogene Proteins c-myc / genetics*
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Rosaceae / chemistry
  • Triterpenes / chemistry
  • Triterpenes / pharmacology*


  • Antineoplastic Agents, Phytogenic
  • Biomarkers
  • Biomarkers, Tumor
  • CD24 Antigen
  • Hyaluronan Receptors
  • Proto-Oncogene Proteins c-myc
  • Triterpenes