Wogonin inhibits LPS-induced tumor angiogenesis via suppressing PI3K/Akt/NF-κB signaling.

Abstract

Wogonin has been shown to have anti-angiogenesis and anti-tumor effects. However, whether wogonin inhibits LPS-induced tumor angiogenesis is not well known. In this study, we investigated the effect of wogonin on inhibiting LPS-induced tumor angiogenesis and further probed the underlying mechanisms. ELISA results revealed that wogonin could suppress LPS-induced VEGF secretion from tumor cells. Transwell assay, tube formation assay, rat aortic ring assay and CAM model were used to evaluate the effect of wogonin on angiogenesis induced by MCF-7 cell (treated with LPS) in vitro and in vivo. The inhibitory effect of wogonin on angiogenesis in LPS-treated MCF-7 cells was then confirmed by the above in vitro and in vivo assays. The study of the molecular mechanism showed that wogonin could suppress PI3K/Akt signaling activation. Moreover, wogonin inhibited nuclear translocation of NF-κB and its binding to DNA. The result of real-time PCR and luciferase reporter assay suggested that VEGF expression was down-regulated by wogonin primarily at the transcriptional level. IGF-1 and p65 expression plasmid were used to activate PI3K/Akt and NF-κB pathways, and to observe the effect of wogonin on the simualtion of PI3K/Akt/NF-κB signaling. Taken together, the result suggested that wogonin was a potent inhibitor of tumor angiogenesis and provided a new insight into the mechanisms of wogonin against cancer.

• Authors: Kai Zhao, Xiuming Song, Yujie Huang, Jing Yao, Mi Zhou, Zhiyu Li, Qidong You, Qinglong Guo, Na Lu
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 737 Pg. 57-69 (Aug 15 2014) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 24858369 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents
• Flavanones
• Lipopolysaccharides
• NF-kappa B
• TLR4 protein, human
• Toll-Like Receptor 4
• Vascular Endothelial Growth Factor A
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• wogonin

Topics

• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Flavanones (pharmacology, therapeutic use)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Lipopolysaccharides (adverse effects)
• NF-kappa B (metabolism)
• Neoplasms (blood supply)
• Neovascularization, Pathologic (drug therapy)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats
• Signal Transduction (drug effects)
• Toll-Like Receptor 4 (metabolism)
• Vascular Endothelial Growth Factor A (genetics, metabolism)