Norcantharidin inhibits tumor angiogenesis via blocking VEGFR2/MEK/ERK signaling pathways.

Abstract

Norcantharidin (NCTD), the demethylated form of Cantharidin, a reagent isolated from blister beetles, has been shown to be an anti-tumor agent capable of inhibiting proliferation as well as inducing apoptosis in many cancer cell lines. However, little is known about the effect of NCTD in tumor angiogenesis. In this study, we demonstrated that NCTD inhibited vascular endothelial growth factor (VEGF)-induced cell proliferation, migration, invasion, and capillary tube formation of primary human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner. Furthermore, we showed NCTD inhibited tumor growth and angiogenesis of colon cancer cells (LOVO) in vivo. We then mechanistically described that NCTD specifically abrogated the phosphorylation/activation of vascular endothelial growth factor receptor-2 (VEGFR2)/MEK/ERK pathway kinases, with little effect on the phosphorylation of p38 MAPK and Akt, and on Cox-2 expression. In summary, our results indicate that NCTD is a potential inhibitor of tumor angiogenesis by blocking VEGFR2/MEK/ERK signaling.

• Authors: Long Zhang, Qing Ji, Xuan Liu, Xingzhu Chen, Zhaohua Chen, Yanyan Qiu, Jian Sun, Jianfeng Cai, Huirong Zhu, Qi Li
• Journal: Cancer science (Cancer Sci) Vol. 104 Issue 5 Pg. 604-10 (May 2013) ISSN: 1349-7006 [Electronic] England
• PMID: 23363445 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 Japanese Cancer Association.

Chemical References

• Angiogenesis Inhibitors
• Bridged Bicyclo Compounds, Heterocyclic
• norcantharidin
• Cyclooxygenase 2
• PTGS2 protein, human
• Vascular Endothelial Growth Factor Receptor-2
• Proto-Oncogene Proteins c-akt
• p38 Mitogen-Activated Protein Kinases

Topics

• Angiogenesis Inhibitors (pharmacology)
• Animals
• Bridged Bicyclo Compounds, Heterocyclic (pharmacology)
• Cell Line, Tumor
• Cell Movement (drug effects, genetics)
• Cell Proliferation (drug effects)
• Colorectal Neoplasms (blood supply, drug therapy)
• Cyclooxygenase 2 (genetics, metabolism)
• Human Umbilical Vein Endothelial Cells (drug effects, metabolism, pathology)
• Humans
• MAP Kinase Signaling System (drug effects)
• Male
• Mice
• Mice, SCID
• Neoplasm Invasiveness
• Neovascularization, Pathologic (drug therapy, genetics, metabolism, pathology)
• Phosphorylation
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Signal Transduction (drug effects, genetics)
• Vascular Endothelial Growth Factor Receptor-2 (genetics, metabolism)
• Xenograft Model Antitumor Assays
• p38 Mitogen-Activated Protein Kinases (genetics, metabolism)