The Anti-Angiogenic and Anti-Proliferative Activity of Methyl Hydroxychalcone

OBJECTIVE: Angiogenesis plays a key role in tumor growth, invasion, and metastasis of cancer diseases, and therefore, the inhibition of angiogenesis can provide an important therapeutic approach in cancer diseases. The aim of this study was to investigate the inhibitory effects of methyl hydroxychalcone on ex vivo sprouting of rat aortic micro-vessels and in vivo formation of chorionic plexus in chick chorioallantoic membrane and to investigate the mechanism underlying anti-angiogenic activity. METHODS: Rat aortic rings were sectioned by 1 mm. 500μl of 3 mg/ml of fibrinogen in serum free M199 growth medium was added to each well with 5 ug/ml of aprotinin. Methyl hydroxychalcone at varying concentrations ranging from 6.25 µg/ml to 100 µg/ml was added to the complete growth medium. Fertilized chicken eggs were incubated at 37°C. On day 3, a small window was opened in the shell. The window was sealed with adhesive tape and incubated until day 5. One mg of methylhydroxychalcone was applied. Images of each CAM were captured using a digital camera, and the dimensions of the blood vessels were measured digitally. Vascular endothelial growth factor (VEGF)-induced human umbilical vein endothelial cell (HUVEC) proliferation and tube formation assays were examined. Additionally, VEGF-165 levels and expression of membrane VEGF receptor-2 in HUVEC lysates have been assessed. RESULTS: The data showed that methyl hydroxychalcone significantly had antiangiogenic activity in a dose dependent manner in the rat aorta assay and had significant perturbation activity on blood vessels in the CAM assay. Methyl hydroxychalcone significantly inhibited proliferation and capillary-like tube formation in VEGF-induced HUVEC. Moreover, methylhydroxychalcone significantly reduced VEGF-165 levels in HUVECs lysate. CONCLUSION: This study showed that methyl hydroxychalcone significantly inhibits the angiogenesis process, blocking the VEGF signaling pathway in HUVECs and could be a potential promising angiogenesis inhibitor lead compound.