Betavulgarin Isolated from Sugar Beet (Beta vulgaris) Suppresses Breast Cancer Stem Cells through Stat3 Signaling

Molecules. 2020 Jun 30;25(13):2999. doi: 10.3390/molecules25132999.


Breast cancer is a major health problem that affects lives worldwide. Breast cancer stem cells (BCSCs) are small subpopulations of cells with capacities for drug resistance, self-renewal, recurrence, metastasis, and differentiation. Herein, powder extracts of beetroot were subjected to silica gel, gel filtration, thin layer chromatography (TLC), and preparatory high-pressure liquid chromatography (HPLC) for isolation of one compound, based on activity-guided purification using tumorsphere formation assays. The purified compound was identified as betavulgarin, using nuclear magnetic resonance spectroscopy and electrospray ionization (ESI) mass spectrometry. Betavulgarin suppressed the proliferation, migration, colony formation, and mammosphere formation of breast cancer cells and reduced the size of the CD44+/CD24- subpopulation and the expression of the self-renewal-related genes, C-Myc, Nanog, and Oct4. This compound decreased the total level and phosphorylated nuclear level of signal transducer and activator of transcription 3 (Stat3) and reduced the mRNA and protein levels of sex determining region Y (SRY)-box 2 (SOX2), in mammospheres. These data suggest that betavulgarin inhibit the Stat3/Sox2 signaling pathway and induces BCSC death, indicating betavulgarin might be an anticancer agent against breast cancer cells and BCSCs.

Keywords: SOX2; Stat3; betavulgarin; breast cancer stem cells (BCSCs); mammospheres.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Apoptosis
  • Benzopyrans / pharmacology*
  • Benzopyrans / therapeutic use
  • Beta vulgaris / chemistry*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Plant Extracts / pharmacology*
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects
  • Tumor Cells, Cultured


  • Antineoplastic Agents, Phytogenic
  • Benzopyrans
  • Plant Extracts
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • betavulgarin