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ZFIN ID: ZDB-PUB-110214-9
5-formylhonokiol exerts anti-angiogenesis activity via inactivating the ERK signaling pathway
Zhu, W., Fu, A., Hu, J., Wang, T., Luo, Y., Peng, M., Ma, Y., Wei, Y., and Chen, L.
Date: 2011
Source: Experimental & molecular medicine   43(3): 146-52 (Journal)
Registered Authors: Hu, Jia
Keywords: 5-formylhonokiol, angiogenesis, ERK pathway, cell migration, cystoskeleton
MeSH Terms:
  • Actins/metabolism
  • Angiogenesis Inhibitors/pharmacology*
  • Animals
  • Antineoplastic Agents, Phytogenic/pharmacology
  • Biphenyl Compounds/pharmacology*
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement/drug effects
  • Cell Proliferation/drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/metabolism
  • Endothelium, Vascular/drug effects*
  • Endothelium, Vascular/metabolism
  • Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors*
  • Extracellular Signal-Regulated MAP Kinases/metabolism
  • Humans
  • Lignans/pharmacology*
  • Neovascularization, Physiologic/drug effects*
  • Signal Transduction/drug effects*
  • Umbilical Veins/cytology
  • Wound Healing
  • Zebrafish/embryology
  • Zebrafish/metabolism
PubMed: 21297378 Full text @ Exp. Mol. Med.
Our previous report has demonstrated that 5-formylhonokiol (FH), a derivative of honokiol (HK), exerts more potent anti-proliferative activities than honokiol in several tumor cell lines. In present study, we first explored the antiangiogenic activities of 5-formylhonokiol on proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs) for the first time in vitro. Then we investigated the in vivo antiangiogenic effect of 5-formylhonokiol on zebrafish angiogenesis model. In order to clarify the underlying molecular mechanism of 5-formylhonokiol, we investigated the signaling pathway involved in controlling the angiogenesis process by western blotting assay. Wound-healing results showed that 5-formylhonokiol significantly and dose-dependently inhibited migration of cultured human umbilical vein enthothelial cells. The invasiveness of HUVEC cells was also effectively suppressed at a low concentration of 5-formylhonokiol in the transwell assay. Further F-actin imaging revealed that inhibitory effect of 5-formylhonokiol on invasion may partly contribute to the disruption on assembling stress fiber. Tube formation assay, which is associated with endothelial cells migration, further confirmed the anti-angiogenesis effect of 5-formylhonokiol. In vivo on zebrafish angiogenesis model, we found that 5-formylhonokiol dose-dependently inhibited angiogenesis. Furthermore, western blotting showed that 5-formylhonokiol significantly down-regulated extracellular signal-regulated kinase (ERK) expression and inhibited the phosphorylation of ERK but not affecting the total protein kinase B (Akt) expression and related phosphorylation, suggesting that 5-formylhonokiol might exert anti-angiogenesis capacity via down-regulation of the ERK signal pathway. Take together, these data suggested that 5-formylhonokiol might be a viable drug candidate in antiangiogenesis and anticancer therapies.