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Molecules 2017, 22(1), 126;

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

Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, China
Key Laboratory of Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou 510632, China
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)
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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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