Capsaicin Inhibits in Vitro and in Vivo Angiogenesis

Jeong Ki Min, Kyu Yeon Han, Eok Cheon Kim, Young Myeong Kim, Sae Won Lee, Ok Hee Kim, Kyu Won Kim, Yong Song Gho, Young Guen Kwon

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162 Citations (Scopus)

Abstract

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), a natural product of Capsicum species, is known to induce excitation of nociceptive terminals involved in pain perception. Recent studies have also shown that capsaicin not only has chemopreventive properties against certain carcinogens and mutagens but also exerts anticancer activity. Here, we demonstrated the antiangiogenic activity of capsaicin using in vitro and in vivo assay systems. In vitro, capsaicin inhibited vascular endothelial growth factor (VEGF)-induced proliferation, DNA synthesis, chemotactic motility, and capillary-like tube formation of primary cultured human endothelial cells. Capsaicin inhibited both VEGF-induced vessel sprouting in rat aortic ring assay and VEGF-induced vessel formation in the mouse Matrigel plug assay. Moreover, capsaicin was able to suppress tumor-induced angiogenesis in chick chorioallantoic membrane assay. Capsaicin caused G1 arrest in endothelial cells. This effect correlated with the down-regulation of the expression of cyclin D1 that led to inhibition of cyclin-dependent kinase 4-mediated phosphorylation of retinoblastoma protein. Signaling experiments show that capsaicin inhibits VEGF-induced p38 mitogen-activated protein kinase, p125FAK, and AKT activation, but its molecular target is distinct from the VEGF receptor KDR/Flk-1. Taken together, these results demonstrate that capsaicin is a novel inhibitor of angiogenesis and suggest that it may be valuable to develop pharmaceutical drugs for treatment of angiogenesis-dependent human diseases such as tumors.

Original languageEnglish
Pages (from-to)644-651
Number of pages8
JournalCancer Research
Volume64
Issue number2
DOIs
Publication statusPublished - 2004 Jan 15

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Min, J. K., Han, K. Y., Kim, E. C., Kim, Y. M., Lee, S. W., Kim, O. H., Kim, K. W., Gho, Y. S., & Kwon, Y. G. (2004). Capsaicin Inhibits in Vitro and in Vivo Angiogenesis. Cancer Research, 64(2), 644-651. https://doi.org/10.1158/0008-5472.CAN-03-3250