Myricetin Inhibits Breast Tumor Growth and Angiogenesis by Regulating VEGF/VEGFR2 and p38MAPK Signaling Pathways

Anat Rec (Hoboken). 2019 Dec;302(12):2186-2192. doi: 10.1002/ar.24222. Epub 2019 Jul 17.

Abstract

Tumor angiogenesis is an important cause of tumor growth and metastasis. Myricetin is a flavonoid component used in traditional Chinese medicine that has been demonstrated to have anticancer activity. However, to the best of our knowledge, the effect of myricetin on tumor angiogenesis remains unknown. The present study reports the identification of myricetin as a potential chemopreventive agent by reason of its inhibition of tumor angiogenesis and demonstrates the anticancer effects of myricetin in vivo. Cell Counting Kit-8 assays revealed that myricetin inhibits the proliferation of tumor cells but not that of human umbilical vein endothelial cells (HUVECs), and a transwell assay demonstrated that myricetin could inhibit the migration of HUVECs. A rat aortic ring assay revealed that myricetin could also affect the development of microvessels and the formation of vascular networks. Further, an ELISA showed that myricetin reduced the levels of vascular endothelial growth factor (VEGF) in vivo and in vitro. Western blot analysis indicated that myricetin could downregulate VEGFR2 and p38MAPK. Therefore, myricetin could significantly inhibit tumor angiogenesis and has potential as a chemopreventive agent because of its inhibition to angiogenesis. Anat Rec, 302:2186-2192, 2019. © 2019 American Association for Anatomy.

Keywords: VEGF; VEGFR2; angiogenesis; antitumor; myricetin; p38MAPK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Proliferation
  • Female
  • Flavonoids / pharmacology*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism*
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism*
  • Xenograft Model Antitumor Assays
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Biomarkers, Tumor
  • Flavonoids
  • Vascular Endothelial Growth Factor A
  • myricetin
  • Vascular Endothelial Growth Factor Receptor-2
  • p38 Mitogen-Activated Protein Kinases