Inhibition of angiogenesis and invasion by DMBT is mediated by downregulation of VEGF and MMP-9 through Akt pathway in MDA-MB-231 breast cancer cells

Invasion, either directly or via metastasis formation, is the main cause of death in cancer patients, development of efficient anti-invasive agents is an important research challenge. In order to obtain more potent inhibitors, a series of brartemicin analogs were synthesized and evaluated for their inhibitory activity against invasion. Among the synthetic analogs tested, DMBT, 6,6'-bis (2,3-dimethoxybenzoyl)-a,a-n-trehalose, was found to be the most potent anti-invasive agent. But the effects of DMBT on breast cancer cells were not known. In this study, the effects of DMBT on invasion and metastasis in MDA-MB-231 cells were investigated. MTT assay showed that no obvious inhibitory or cytotoxic effect of DMBT was found. DMBT could inhibit invasion, migration and tube formation of HUVECs. Gelatin zymography showed that DMBT inhibited secretion and activity of MMP-9. Western blotting demonstrated that DMBT effectively suppressed the expression of VEGF, p-VEGFR-2, p-EGFR, and p-Akt. These results suggested that DMBT could inhibit invasion and angiogenesis by downregulation of VEGF and MMP-9, resulting from the inhibition of Akt pathway. DMBT might be a promising lead molecule for the anti-metastasis and serve as a therapeutic agent to inhibit breast cancer cell invasion and metastasis. (C) 2013 Elsevier Ltd. All rights reserved.