Anti-angiogenic properties of artemisinin derivatives (Review)

Int J Mol Med. 2017 Oct;40(4):972-978. doi: 10.3892/ijmm.2017.3085. Epub 2017 Jul 31.

Abstract

Angiogenesis, the process involving the development of new blood vessels from existing capillaries, is critical for growth and wound healing. However, pathological angiogenesis contributes to the pathogeneses of numerous diseases, including cancer, rheumatoid arthritis, diabetic retinopathy and macular degeneration. Hence, the inhibition of angiogenesis is an effective therapeutic approach for these diseases. Apart from its anti-malarial properties, artemisinin and its derivatives also exhibit potent anti-angiogenic properties. The molecular mechanisms underlying their inhibitory effects on angiogenesis have been studied by several groups. These investigations have revealed that artemisinins inhibit angiogenesis via the perturbations of cellular signaling pathways involved in the regulation of angiogenesis. Along with a brief introduction to artemisinin derivatives, this review provides a detailed summary of the effects of artemisinins on the mitogen-activated protein kinase (MAPK) pathway, the nuclear factor-κB (NF-κB) pathway and the phosphatidylinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway. Due to the multiplicity of their actions on relevant signaling pathways, artemisinins are promising candidates with potential for use as anti-angiogenic agents for the treatment of related diseases or disorders.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Artemisinins / pharmacology*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / pathology
  • Disease Models, Animal
  • Gene Expression Regulation, Neoplastic*
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Macular Degeneration / drug therapy*
  • Macular Degeneration / genetics
  • Macular Degeneration / metabolism
  • Macular Degeneration / pathology
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Neoplasms / blood supply
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Angiogenesis Inhibitors
  • Artemisinins
  • NF-kappa B
  • Phosphoinositide-3 Kinase Inhibitors
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-2
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases