Anti-angiogenic properties of artemisinin derivatives (Review).

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.