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Molecules 2017, 22(1), 126; doi:10.3390/molecules22010126

Penduliflaworosin, a Diterpenoid from Croton crassifolius, Exerts Anti-Angiogenic Effect via VEGF Receptor-2 Signaling Pathway

1
Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, China
2
Key Laboratory of Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou 510632, China
3
Department of Developmental & Regenerative Biology, Jinan University, Guangzhou 510632, China
*
Authors to whom correspondence should be addressed.
Academic Editors: Quan-Bin Han and Derek J. McPhee
Received: 20 October 2016 / Revised: 4 January 2017 / Accepted: 4 January 2017 / Published: 13 January 2017
(This article belongs to the Special Issue Diterpene and Its Significance in Natural Medicine)
View Full-Text   |   Download PDF [10384 KB, uploaded 17 January 2017]   |  

Abstract

Anti-angiogenesis targeting vascular endothelial growth factor receptor-2 (VEGFR-2) has been considered as an important strategy for cancer therapy. Penduliflaworosin is a diterpenoid isolated from the plant Croton crassifolius. Our previous study showed that this diterpenoid possesses strong anti-angiogenic activity by inhibiting vessel formation in zebrafish. This study was conducted to further investigate the anti-angiogenic activity and mechanism of penduliflaworosin. Results revealed that penduliflaworosin significantly inhibited VEGF-induced angiogenesis processes including proliferation, invasion, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). Moreover, it notably inhibited VEGF-induced sprout formation of aortic rings and blocked VEGF-induced vessel formation in mice. Western blotting studies showed that penduliflaworosin inhibited phosphorylation of the VEGF receptor-2 and its downstream signaling mediators in HUVECs, suggesting that the anti-angiogenic activity was due to an interference with the VEGF/VEGF receptor-2 pathway. In addition, molecular docking simulation indicated that penduliflaworosin could form hydrogen bonds within the ATP-binding region of the VEGF receptor-2 kinase unit. Finally, cytotoxicity assay showed that penduliflaworosin possessed little toxicity toward both cancer and normal cells. Taken together, our findings demonstrate that penduliflaworosin exerts its anti-angiogenic effect via the VEGF receptor-2 signaling pathway. The anti-angiogenic property and low cytotoxicity of penduliflaworosin suggest that it may be useful in cancer treatments. View Full-Text
Keywords: penduliflaworosin; anti-angiogenesis; VEGF receptor-2 penduliflaworosin; anti-angiogenesis; VEGF receptor-2
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Liang, Y.; Zhang, Y.; Wang, G.; Li, Y.; Huang, W. Penduliflaworosin, a Diterpenoid from Croton crassifolius, Exerts Anti-Angiogenic Effect via VEGF Receptor-2 Signaling Pathway. Molecules 2017, 22, 126.

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