PUBLICATION

Dietary compound glycyrrhetinic acid suppresses tumor angiogenesis and growth by modulating antiangiogenic and proapoptotic pathways in vitro and in vivo

Authors
Li, J., Tang, F., Li, R., Chen, Z., Lee, S.M., Fu, C., Zhang, J., Leung, G.P.
ID
ZDB-PUB-191213-15
Date
2019
Source
The Journal of Nutritional Biochemistry   77: 108268 (Journal)
Registered Authors
Keywords
Antiangiogenesis, Apoptosis, Dietary compound, Glycyrrhetinic acid, Ovarian cancer
MeSH Terms
  • Animals
  • Aorta/metabolism
  • Apoptosis/drug effects*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Female
  • Glycyrrhetinic Acid/pharmacology*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Membrane Potential, Mitochondrial
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness
  • Neovascularization, Pathologic/prevention & control*
  • Ovarian Neoplasms/drug therapy*
  • Ovarian Neoplasms/prevention & control*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Xenograft Model Antitumor Assays
  • Zebrafish
PubMed
31830590 Full text @ J. Nutr. Biochem.
Abstract
Glycyrrhetinic acid (GA) is a major bioactive compound of licorice. The objective of this study was to investigate the effects of GA on ovarian cancer, particularly those related to angiogenesis and apoptosis, and to elucidate the underlying mechanisms of action. In vitro studies showed that GA significantly inhibited proliferation, migration, invasion and tube formation in human umbilical vein endothelial cells (HUVECs) in a concentration-dependent manner. GA inhibited the phosphorylation of major receptors and enzymes involved in angiogenesis, such as VEGFR2, mTOR, Akt, ERK1/2, MEK1/2, p38 and JNK1/2 in HUVECs. In addition, GA induced apoptosis, loss of mitochondrial membrane potential and cell cycle arrest in G1 phase in A2780 ovarian cancer cells. The proapoptotic effect of GA involved the increased phosphorylation of p38 and JNK1/2; increased cleavage of caspase 3, caspase 9 and PARP; reduced phosphorylation of mTOR, Akt and ERK1/2; and reduced expressions of survivin and cyclin D1. Ex vivo studies showed that GA significantly inhibited microvessel sprouting in rat aortic ring model. In vivo studies showed that GA inhibited the formation of new blood vessels in zebrafish and mouse Matrigel plug. GA also significantly reduced the size of ovarian cancer xenograft tumors in nude mice. Taken together, GA possesses potential antitumor effects, and the underlying mechanisms may involve the inhibition of signaling pathways related to angiogenesis and the activation of apoptotic pathways in cancer cells. Our findings suggest that GA could serve as an effective regimen in the prevention or treatment of cancer.
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