PUBLICATION
5-formylhonokiol exerts anti-angiogenesis activity via inactivating the ERK signaling pathway
- Authors
- Zhu, W., Fu, A., Hu, J., Wang, T., Luo, Y., Peng, M., Ma, Y., Wei, Y., and Chen, L.
- ID
- ZDB-PUB-110214-9
- 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.
Citation
Zhu, W., Fu, A., Hu, J., Wang, T., Luo, Y., Peng, M., Ma, Y., Wei, Y., and Chen, L. (2011) 5-formylhonokiol exerts anti-angiogenesis activity via inactivating the ERK signaling pathway. Experimental & molecular medicine. 43(3):146-52.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
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