Betulinic Acid Kills Colon Cancer Stem Cells

Curr Stem Cell Res Ther. 2016;11(5):427-33. doi: 10.2174/1574888x11666151203223512.

Abstract

Cancer stem cells (CSCs) are considered to be the origin of cancer and it is suggested that they are resistant to chemotherapy. Current therapies fail to eradicate CSCs and therefore selecting a resistant cell subset that is able to facilitate tumor recurrences. Betulinic acid (BetA) is a broad acting natural compound, shown to induce cell death via the inhibition of the stearoyl-CoA- desaturase (SCD- 1). This enzyme converts saturated fatty acids into unsaturated fatty acids and is over-expressed in tumor cells. Here we show that BetA induces rapid cell death in all colon CSCs tested and is able to affect the CSCs directly as shown, via the loss of clonogenic capacity. Similar results were observed with inhibition of SCD-1, suggesting that SCD-1 activity is indeed a vulnerable link in colon CSCs and can be considered an ideal target for therapy in colon cancer.

MeSH terms

  • Cell Death / drug effects
  • Cell Line, Tumor
  • Clone Cells
  • Colonic Neoplasms / enzymology
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology*
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Mutation / genetics
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / pathology*
  • Pentacyclic Triterpenes
  • Stearoyl-CoA Desaturase / antagonists & inhibitors
  • Stearoyl-CoA Desaturase / metabolism
  • Triterpenes / pharmacology*

Substances

  • Enzyme Inhibitors
  • Pentacyclic Triterpenes
  • Triterpenes
  • betulinic acid
  • Stearoyl-CoA Desaturase