Machilin D, a Lignin Derived from Saururus chinensis, Suppresses Breast Cancer Stem Cells and Inhibits NF-κB Signaling

Biomolecules. 2020 Feb 5;10(2):245. doi: 10.3390/biom10020245.

Abstract

Cancer stem cells are responsible for breast cancer initiation, metastasis, and relapse. Targeting breast cancer stem cells (BCSCs) using phytochemicals is a good strategy for the treatment of cancer. A silica gel, a reversed-phase C18 column (ODS), a Sephadex LH-20 gel, thin layer chromatography, and high-performance liquid chromatography (HPLC) were used for compound isolation from Saururus chinensis extracts. The isolated compound was identified as machilin D by mass spectrometry and nuclear magnetic resonance (NMR). Machilin D inhibited the growth and mammosphere formation of breast cancer cells and inhibited tumor growth in a xenograft mouse model. Machilin D reduced the proportions of CD44+/CD24- and aldehyde dehydrogenase 1 (ALDH1)-positive cells. Furthermore, this compound reduced the nuclear localization of the NF-κB protein and decreased the IL-6 and IL-8 secretion in mammospheres. These results suggest that machilin D blocks IL-6 and IL-8 signaling and induces CSC death and thus may be a potential agent targeting BCSCs.

Keywords: NF-κB; breast cancer stem cells (BCSCs); machilin D; mammospheres.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Aldehyde Dehydrogenase 1 Family / metabolism
  • Animals
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • CD24 Antigen / metabolism
  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid
  • Chromatography, Thin Layer
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hyaluronan Receptors / metabolism
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Lignans / pharmacology*
  • MCF-7 Cells
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Mice
  • Mice, Nude
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Neoplasm Transplantation
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism
  • Plant Extracts / chemistry
  • Powders
  • Saururaceae / chemistry*
  • Signal Transduction / drug effects*

Substances

  • CD24 Antigen
  • CD24 protein, human
  • CD44 protein, human
  • CXCL8 protein, human
  • Hyaluronan Receptors
  • IL6 protein, human
  • Interleukin-6
  • Interleukin-8
  • Lignans
  • NF-kappa B
  • Plant Extracts
  • Powders
  • machilin D
  • Aldehyde Dehydrogenase 1 Family