Piperine, a dietary phytochemical, inhibits angiogenesis

J Nutr Biochem. 2013 Jan;24(1):231-9. doi: 10.1016/j.jnutbio.2012.05.009. Epub 2012 Aug 16.


Angiogenesis plays an important role in tumor progression. Piperine, a major alkaloid constituent of black pepper, has diverse physiological actions including killing of cancer cells; however, the effect of piperine on angiogenesis is not known. Here we show that piperine inhibited the proliferation and G(1)/S transition of human umbilical vein endothelial cells (HUVECs) without causing cell death. Piperine also inhibited HUVEC migration and tubule formation in vitro, as well as collagen-induced angiogenic activity by rat aorta explants and breast cancer cell-induced angiogenesis in chick embryos. Although piperine binds to and activates the cation channel transient receptor potential vanilloid 1 (TRPV1), its effects on endothelial cells did not involve TRPV1 since the antiproliferative effect of piperine was not affected by TRPV1-selective antagonists, nor did HUVECs express detectable TRPV1 mRNA. Importantly, piperine inhibited phosphorylation of Ser 473 and Thr 308 residues of Akt (protein kinase B), which is a key regulator of endothelial cell function and angiogenesis. Consistent with Akt inhibition as the basis of piperine's action on HUVECs, inhibition of the phosphoinositide-3 kinase/Akt signaling pathway with LY-294002 also inhibited HUVEC proliferation and collagen-induced angiogenesis. Taken together, these data support the further investigation of piperine as an angiogenesis inhibitor for use in cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology*
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Aorta / drug effects
  • Benzodioxoles / pharmacology*
  • Breast Neoplasms / blood supply
  • Breast Neoplasms / drug therapy
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Chick Embryo
  • Chromones / pharmacology
  • Drug Screening Assays, Antitumor / methods
  • Female
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • In Vitro Techniques
  • Male
  • Morpholines / pharmacology
  • Neovascularization, Pathologic / drug therapy*
  • Phosphorylation / drug effects
  • Piperidines / pharmacology*
  • Polyunsaturated Alkamides / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats, Wistar
  • S Phase / drug effects
  • Serine / metabolism
  • TRPV Cation Channels / genetics
  • Threonine / metabolism


  • Alkaloids
  • Angiogenesis Inhibitors
  • Benzodioxoles
  • Chromones
  • Morpholines
  • Piperidines
  • Polyunsaturated Alkamides
  • TRPV Cation Channels
  • TRPV1 protein, human
  • Threonine
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Serine
  • Proto-Oncogene Proteins c-akt
  • piperine

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