marmesin and Lung-Neoplasms

In the present study, we investigated the effects and molecular mechanism of marmesin, a natural coumarin compound isolated from Broussonetia kazinoki, on non-small cell lung cancer (NSCLC) cell responses and tumor angiogenesis. Marmesin abrogated mitogen-stimulated proliferation and invasion in both p53 wild-type A549 and p53-deficient H1299 NSCLC cells. These antitumor activities of marmesin were mediated by the inactivation of mitogenic signaling pathways and downregulation of cell signaling-related proteins including vascular endothelial growth factor receptor-2 (VEGFR-2), integrin β1, integrin-linked kinase and matrix metalloproteinases-2. Furthermore, marmesin suppressed the expression and secretion of VEGF in both NSCLC cells, leading to inhibition of capillary-like structure formation in human umbilical vein endothelial cells. Collectively, these findings demonstrate the pharmacological roles and molecular targets of marmesin in regulating NSCLC cell responses and tumor angiogenesis.

Topics: A549 Cells; Carcinoma, Non-Small-Cell Lung; Cells, Cultured; Coumarins; Down-Regulation; Gene Expression Regulation, Neoplastic; Human Umbilical Vein Endothelial Cells; Humans; Integrin beta1; Lung Neoplasms; Neovascularization, Pathologic; Receptors, Vascular Endothelial Growth Factor; Vascular Endothelial Growth Factor A