High-throughput screening identifies artesunate as selective inhibitor of cancer stemness: Involvement of mitochondrial metabolism

Biochem Biophys Res Commun. 2016 Sep 2;477(4):737-742. doi: 10.1016/j.bbrc.2016.06.128. Epub 2016 Jun 27.

Abstract

Cancer stem cells (CSCs) have robust systems to maintain cancer stemness and drug resistance. Thus, targeting such robust systems instead of focusing on individual signaling pathways should be the approach allowing the identification of selective CSC inhibitors. Here, we used the alkaline phosphatase (ALP) assay to identify inhibitors for cancer stemness in induced cancer stem-like (iCSCL) cells. We screened several compounds from natural product chemical library and evaluated hit compounds for their efficacy on cancer stemness in iCSCL tumorspheres. We identified artesunate, an antimalarial drug, as a selective inhibitor of cancer stemness. Artesunate induced mitochondrial dysfunction that selectively inhibited cancer stemness of iCSCL cells, indicating an essential role of mitochondrial metabolism in cancer stemness.

Keywords: Artesunate; CSCs; High-throughput screening; Mitochondrial metabolism; Tumorspheres.

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Apoptosis / drug effects
  • Artemisinins / administration & dosage*
  • Artesunate
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor / methods
  • High-Throughput Screening Assays / methods*
  • Humans
  • Mitochondria / drug effects*
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / metabolism
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / ultrastructure

Substances

  • Antineoplastic Agents
  • Artemisinins
  • Mitochondrial Proteins
  • Artesunate