β-Cryptoxanthin Inhibits Angiogenesis in Human Umbilical Vein Endothelial Cells Through Retinoic Acid Receptor

Mol Nutr Food Res. 2018 Jan;62(2). doi: 10.1002/mnfr.201700489. Epub 2017 Dec 29.

Abstract

Scope: β-Cryptoxanthin is an abundant carotenoid in fruits and vegetables that can be quantified in human blood serum. Yet, contrary to other carotenoids, its effects on endothelial cells and angiogenesis remain unknown.

Methods and results: Human umbilical vein endothelial cells (HUVEC) are treated with 0.01, 0.1, or 1 μm of β-cryptoxanthin. Antioxidant activity is determined by its free radical scavenging and oxygen-radical absorbance capacity. The effect on migration and formation of tubular structures is studied. Additionally, effect on angiogenesis is also analyzed using an in vivo model. β-Cryptoxanthin exhibits scavenging ability, having an antioxidant effect on HUVEC. Interestingly, β-cryptoxanthin reduces their migration and angiogenesis, even in the presence of vascular endothelial growth factor (VEGF). Additionally, such carotenoid inhibits in vivo angiogenesis induced by VEGF. In addition, treatment of HUVEC with LE540 (retinoic acid receptor [RAR] panantagonist) inhibits β-cryptoxanthin antiangiogenic effect on HUVEC.

Conclusion: β-Cryptoxanthin inhibits angiogenesis through RAR. Thus, this carotenoid and food containing it may be useful for the prevention and treatment of angiogenic pathologies. That includes tumoral growth and wet macular degeneration associated with aging. To the best of our knowledge, this is the first report of the antioxidant effect and antiangiogenic activity of this carotenoid on HUVEC, both in vitro and in vivo.

Keywords: angiogenesis; antioxidant; carotenoids; retinoic acid receptors; β-cryptoxanthin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Antioxidants / pharmacology
  • Beta-Cryptoxanthin / pharmacology*
  • Cell Movement / drug effects
  • Dibenzazepines / pharmacology
  • Gene Expression Regulation / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Mice, Inbred C57BL
  • Neovascularization, Physiologic / drug effects*
  • Neovascularization, Physiologic / genetics
  • Receptors, Retinoic Acid / metabolism*
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor A / pharmacology

Substances

  • Angiogenesis Inhibitors
  • Antioxidants
  • Beta-Cryptoxanthin
  • Dibenzazepines
  • LE 540
  • Receptors, Retinoic Acid
  • Vascular Endothelial Growth Factor A