Effects of Evodiamine on the Expression and Secretion of Vascular Endothelial Growth Factor in Human Breast Cancer Cells.

Abstract

It has been well-known that the breast cancer is related to westernize of the diet and the life, the menopause time delay and the environmental pollution. In the recent years, many scientists devoted to the research and the development of new anti-cancer drugs. Evodiamine was one of the major bioactive compounds isolated and puried from Chinese medicine, Wu-Chu-Yu. It has been demonstrated that evodiamine causes the vasodilatation, uterus contraction and anti-inflammation effects. The evodiamine has been shown to have the ability on the suppression of the growth, the migration, the metastasis and growth factor secretion in many kinds of cancer cells. Angiogenesis is the growth of new vascular capillary from pre-existing vessels. Vascular endothelial growth factor ( VEGF ), the potent angiogenic factor, can stimulate endothelial cell proliferation and migration, and is responsible for vascular leakage and metastasis in the tumor. The purpose of this study was to investigate the effects of evodiamine ( 0.1 ~ 10 μM ) on the secretion of VEGF in human breast cancer cells, MCF-7, and the effects of evodiamine on the secretion of VEGF in CoCl2 ( a hypoxia-mimicking agent ) and heregulin ( HRG, the activator of human epithelial cell growth factor receptor ) stimulated tumor cells. MCF-7 cells were incubated in different concentrations of evodiamine for 24 h to observe the cell morphology. Analysis using the western blotting and the emzyme-linked immunosorbent assay to examine the expression and the secretion of VEGF. CoCl2 and heregulin was used to induce VEGF overexpression, and to examine whether the evodiamine could suppress CoCl2 and heregulin-induced VEGF secretion. After treatment with evodiamine ( 0.1 ~ 10 μM ) for 24 h, the tumor growth was measured by MTT assay. The cell growth in the group treated with 10 μM evodiamine was suppressed. By increasing concentration of evodiamine, the cell morphology became roundness. Compared with the untreated control group, 1 μM evodiamine was significantly to suppress the expression and secretion of VEGF. CoCl2-treated alone was able to increase the secretion of VEGF. However, the evodiamine was unable to suppress CoCl2-induced VEGF release. Heregulin activated the human epithelial growth factor receptor to increase the VEGF release. Evodiamine was able to suppress heregulin-induced VEGF release. The present data indicated that the evodiamine had the inhibitory action on the expression and secretion of VEGF in the human breast cancer cells. These results demonstrated that evodiamine suppressed the expression and secretion of the VEGF in the human breast cancer cell. We suggested that evodiamine offered a new strategy for anti-angiogenesis in breast cancer.