Angiogenesis is the process of generating new capillary of blood vessels from an existing vasculature that plays a vital role in tumor growth and metastasis. Binding of vascular endothelial growth factor (VEGF) to tyrosine kinase receptor (VEGFR) is an important step for initiating vasculogenesis via. transphosphorylation of VEGF receptor associated tyrosine kinase. Therefore, blocking VEGFR or associated kinases has become a common strategy for arresting tumor angiogenesis. The newly discovered JFD is a novel anti-angiogenic agent that can limit the angiogenic capacity of endothelial cells and block tumor angiogenesis. The In vitro anti-angiogenesis potential of JFD was examined by ECMatrigelTM assay with Human umbilical vein endothelial cells (HUVEC) using different concentrations of JFD in the range of 0 - 10 µM. Among the different concentrations used, 1µM JFD significantly inhibited the angiogenesis when compared to control and a complete inhibition was observed at 10 µM concentration. Competitive binding of JFD against Fluorokine labeled VEGF for the same VEGFR was studied at 0.001 - 1.0 µM concentrations of JFD. A dose dependent inhibition of Fluorokine conjugated VEGF binding to its specific receptor in HUVEC cells was confirmed in our study. In the competition binding assay 1.0 µM concentration of JFD caused 93.5% inhibition of conjugated VEGF binding. The same 1.0 µM concentration of JFD was able to inhibit VEGF (10 ng/ml) induced phosphorylation of VEGFR2 in HUVEC cells. Furthermore, the potency of JFD as inhibitor of angiogenesis was experimentally proved by treating athymic nude mice that was implanted with GI-101A (human breast adenocarcinoma) xenograft tumor. Intraperitoneal injection of JFD at 12 mg/kg of body weight was able to significantly inhibit the tumor growth compared to the control group at different time periods. At the end of the treatment period 70% inhibition of tumor growth was observed in JFD treated animals along with prolongation of the survival. The plasma concentrations of JFD was also measured in Balb-C mice at different time periods (0 min - 180 min), using HPLC method. The data from both in vitro and in vivo study provide a strong basis for JFD to be used as a potent anti-angiogenic agent. (The financial support from the Royal Dames of Cancer Research Inc., Ft. Lauderdale, Florida is gratefully acknowledged).

Citation Format: Sivanesan Dhandayuthapani, Appu Rathinavelu. JFD, a novel small molecule for inhibiting vascular endothelial growth factor receptor-mediated angiogenesis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1021. doi:10.1158/1538-7445.AM2014-1021

©2014 American Association for Cancer Research.
2014