5-Formylhonokiol exerts anti-angiogenesis activity via inactivating the ERK signaling pathway.
10.3858/emm.2011.43.3.017
- Author:
Wei ZHU
1
;
Afu FU
;
Jia HU
;
Tianen WANG
;
Youfu LUO
;
Ming PENG
;
Yinghua MA
;
Yuquan WEI
;
Lijuan CHEN
Author Information
1. State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China. lijuan17@hotmail.com
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
angiogenesis inhibitors;
cell movement;
cystoskeleton;
extracellular signal-regulated MAP kinases;
honokiol
- MeSH:
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/metabolism;
Endothelium, Vascular/*drug effects/metabolism;
Extracellular Signal-Regulated MAP Kinases/*antagonists & inhibitors/metabolism;
Humans;
Lignans/*pharmacology;
Neovascularization, Physiologic/*drug effects;
Signal Transduction/*drug effects;
Umbilical Veins/cytology;
Wound Healing;
Zebrafish/embryology/metabolism
- From:Experimental & Molecular Medicine
2011;43(3):146-152
- CountryRepublic of Korea
- Language:English
-
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 of assembling stress fiber. Tube formation assay, which is associated with endothelial cells migration, further confirmed the anti-angiogenesis effect of 5-formylhonokiol. In in vivo 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. Taken together, these data suggested that 5-formylhonokiol might be a viable drug candidate in antiangiogenesis and anticancer therapies.
