Piperine, a dietary phytochemical, inhibits angiogenesis

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...

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Bibliographic Details
Published in:The Journal of nutritional biochemistry 2013-01, Vol.24 (1), p.231-239
Main Authors: Doucette, Carolyn D, Hilchie, Ashley L, Liwski, Robert, Hoskin, David W
Format: Article
Language:English
Subjects:
Alkaloids - pharmacology
angiogenesis
Angiogenesis Inhibitors - pharmacology
Animals
antagonists
aorta
Aorta - drug effects
Benzodioxoles - pharmacology
black pepper
breast neoplasms
Breast Neoplasms - blood supply
Breast Neoplasms - drug therapy
cell death
Cell Movement - drug effects
Cell Proliferation - drug effects
Chick Embryo
chicks
Chromones - pharmacology
Drug Screening Assays, Antitumor - methods
endothelial cells
Female
Human Umbilical Vein Endothelial Cells - drug effects
Human Umbilical Vein Endothelial Cells - metabolism
Humans
In Vitro Techniques
Male
messenger RNA
Morpholines - pharmacology
Neovascularization, Pathologic - drug therapy
phosphorylation
Phosphorylation - drug effects
Piper nigrum
Piperidines - pharmacology
Polyunsaturated Alkamides - pharmacology
protein kinases
Proto-Oncogene Proteins c-akt - metabolism
rats
Rats, Wistar
S Phase - drug effects
Serine - metabolism
Threonine - metabolism
TRPV Cation Channels - genetics
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Summary: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 G₁/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.
ISSN:0955-2863
1873-4847
DOI:10.1016/j.jnutbio.2012.05.009