Sulforaphane synergizes with quercetin to inhibit self-renewal capacity of pancreatic cancer stem cells

Front Biosci (Elite Ed). 2011 Jan 1;3:515-28. doi: 10.2741/e266.

Abstract

According to the cancer stem cell hypothesis, the aggressive growth and early metastasis of cancer may arise through dysregulation of self-renewal of stem cells. The objectives of this study were to examine the molecular mechanisms by which sulforaphane (SFN, an active compound in cruciferous vegetables) inhibits self-renewal capacity of pancreatic cancer stem cells (CSCs), and synergizes with quercetin, a major polyphenol and flavonoid commonly detected in many fruits and vegetables. Our data demonstrated that SFN inhibited self-renewal capacity of pancreatic CSCs. Inhibition of Nanog by lentiviral-mediated shRNA expression enhanced the inhibitory effects of sulforaphane on self-renewal capacity of CSCs. SFN induced apoptosis by inhibiting the expression of Bcl-2 and XIAP, phosphorylation of FKHR, and activating caspase-3. Moreover, SFN inhibited expression of proteins involved in the epithelial-mesenchymal transition (beta-catenin, vimentin, twist-1, and ZEB1), suggesting the blockade of signaling involved in early metastasis. Furthermore, the combination of quercetin with SFN had synergistic effects on self-renewal capacity of pancreatic CSCs. These data suggest that SFN either alone or in combination with quercetin can eliminate cancer stem cell-characteristics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Apoptosis / drug effects*
  • Blotting, Western
  • Cell Line, Tumor
  • Drug Synergism
  • Genetic Vectors / genetics
  • Homeodomain Proteins / antagonists & inhibitors
  • Humans
  • Isothiocyanates
  • Lentivirus
  • Nanog Homeobox Protein
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / physiology
  • Pancreatic Neoplasms / drug therapy*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Quercetin / pharmacology*
  • Thiocyanates / pharmacology*
  • X-Linked Inhibitor of Apoptosis Protein / metabolism

Substances

  • Homeodomain Proteins
  • Isothiocyanates
  • NANOG protein, human
  • Nanog Homeobox Protein
  • Proto-Oncogene Proteins c-bcl-2
  • Thiocyanates
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human
  • Quercetin
  • sulforafan