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PAC-1 and Its Derivative WF-210 Inhibit Angiogenesis by Inhibiting VEGF/VEGFR Pathway

PAC-1 and Its Derivative WF-210 Inhibit Angiogenesis by Inhibiting VEGF/VEGFR Pathway

Fangyang Wang, Lihui Wang, Yi Li, Nannan Wang, Yating Wang, Qi Cao, Ping Gong, Jingyu Yang, Chunfu Wu

Eur J Pharmacol. 2018 Feb 15;821:29-38.

PMID: 29269017

Abstract:

Procaspase Activating Compound-1 (PAC-1) and its derivative WF-210 induce apoptosis in cancer cells by activating procaspase-3 to caspase-3. The aim of this study was to extend current knowledge about the mechanisms of PAC-1 and WF-210, particularly about their effects on tumor angiogenesis. PAC-1 and WF-210 restrained VEGF-induced human umbilical vascular endothelial cells (HUVECs) proliferation, invasion, and tube formation. PAC-1 and WF-210 abrogated VEGF-induced vessel sprouting from rat aortic rings and inhibited vascular formation in the Matrigel plug assay. PAC-1 and WF-210 suppressed phosphorylation of VEGFR2 and its downstream protein kinases c-Src, FAK, and AKT in both HUVECs and U-87 cells. When given to mice bearing subcutaneous or orthotopic xenograft, PAC-1 and WF-210 inhibited the tumor growth and tumor angiogenesis. Further tests showed that PAC-1 and WF-210 inhibited stemness and induced autophagy flux of U-87 cells. This study revealed mechanisms of PAC-1 and WF-210 other than inducing apoptosis, which provides additional support for their using in the clinic.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP315183212	PAC-1		315183-21-2	Price

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