Honokiol, a small molecular weight natural product, inhibits angiogenesis in vitro and tumor growth in vivo

J Biol Chem. 2003 Sep 12;278(37):35501-7. doi: 10.1074/jbc.M302967200. Epub 2003 Jun 19.


Natural products comprise a major source of small molecular weight angiogenesis inhibitors. We have used the transformed endothelial cell line SVR as an effective screen of natural product extracts to isolate anti-angiogenesis and anti-tumor compounds. Aqueous extracts of Magnolia grandiflora exhibit potent activity in our SVR proliferation assays. We found that the small molecular weight compound honokiol is the active principle of magnolia extract. Honokiol exhibited potent anti-proliferative activity against SVR cells in vitro. In addition, honokiol demonstrated preferential inhibition of primary human endothelial cells compared with fibroblasts and this inhibition was antagonized by antibodies against TNF alpha-related apoptosis-inducing ligand. In vivo, honokiol was highly effective against angiosarcoma in nude mice. Our preclinical data suggests that honokiol is a systemically available and non-toxic inhibitor of angiogenesis and should be further evaluated as a potential chemotherapeutic agent.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Apoptosis / drug effects
  • Biphenyl Compounds / pharmacology*
  • Biphenyl Compounds / therapeutic use
  • Cell Division / drug effects
  • Cell Line
  • Cell Line, Transformed
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / transplantation
  • Hemangiosarcoma / drug therapy
  • Hemangiosarcoma / pathology*
  • Humans
  • Lignans*
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology
  • Magnolia
  • Mice
  • Mice, Nude
  • Phytotherapy*
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Transplantation, Heterologous


  • Angiogenesis Inhibitors
  • Biphenyl Compounds
  • Lignans
  • Plant Extracts
  • honokiol