Puerarin 6″-O-xyloside suppresses growth, self-renewal and invasion of lung cancer stem-like cells derived from A549 cells via regulating Akt/c-Myc signalling

Clin Exp Pharmacol Physiol. 2020 Jul;47(7):1311-1319. doi: 10.1111/1440-1681.13294. Epub 2020 Apr 21.

Abstract

Cancer stem cells have been identified as the major cause of cancer initiation and progression. To investigate the effects of puerarin 6″-O-xyloside (PXY), derived from Pueraria lobata (Willd.) Ohwi, on lung cancer stem cells, we enriched and identified a subpopulation of lung cancer stem-like cells (LCSLCs) derived from lung adenocarcinoma A549 cells with traits including high self-renewal and invasive capability in vitro, elevated tumourigenicity in vivo, and high expression of stem cell markers CD44, CD133 and aldehyde dehydrogenase 1 (ALDH1). We found that PXY could impair cell viability, suppress self-renewal and invasive capability, and decrease CD133, CD44 and ALDH1 mRNA expression in LCSLCs in a dose-dependent manner. Furthermore, we showed that PXY suppressed the self-renewal and invasive capability of LCSLCs at least in part through suppressing the activation of Akt/c-Myc signalling. In conclusion, PXY can block the traits of LCSLCs, indicating that PXY may be a candidate compound for lung adenocarcinoma therapy via eliminating LCSLCs.

Keywords: Akt/c-Myc signalling; Puerarin 6″-O-xyloside; cell invasion; lung cancer stem-like cells; self-renewal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Cell Self Renewal / drug effects*
  • Humans
  • Isoflavones / chemistry
  • Isoflavones / pharmacology*
  • Lung Neoplasms / pathology*
  • Neoplasm Invasiveness
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / pathology
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Signal Transduction / drug effects*

Substances

  • Isoflavones
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • Proto-Oncogene Proteins c-akt
  • puerarin