Marmesin-mediated suppression of VEGF/VEGFR and integrin β1 expression: Its implication in non-small cell lung cancer cell responses and tumor angiogenesis

Abstract

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.

The Effect and Mechanism of Vascular Endothelial Growth Fac-tor (VEGF) on Tumor Angiogenesis in Gallbladder Carcinoma

“…The regulation of VEGF by miR-205 had a significant role in promoting the invasion of human ovarian cancer (17). Down regulation of VEGF had an inhibitory effect on lung cancer cell proliferation (18). However, there are few literatures related to the regulation of VEGF in gallbladder carcinoma.…”

Systems Pharmacological Approach to Investigate the Mechanism of Acori Tatarinowii Rhizoma for Alzheimer’s Disease

“…For example, eudesmin (M23; DL=0.62, BBB=0.05, and OB=52.35) was experimentally identified which has anti-inflammation [ 47 ] and anticonvulsion effects [ 48 ]. A angiogenesis inhibitor of marmesin (M28; DL=0.18, BBB=0.07, and OB=50.28) was reported to have regulatory effect on endothelial cell fate and angiogenesis [ 49 ]. Antioxidation and anti-inflammation effect of patchoulene (M31; DL=0.11, BBB=2.17, and OB=49.06) was proved through inhibition of nuclear factor κ B (NF- κ B) and downregulation of COX-2/iNOS [ 50 ].…”

Phytochemical Constituents and Biological Activities of Melicope lunu-ankenda

“…Marmesin, melilunumarin A, and 6-deoxyhaplopinol were found to demonstrate inhibitory effect on TPA-induced EBV-EA activation in Raji cells [ 31 ]. Besides, marmesin inhibits pRb phosphorylation in human umbilical vein endothelial cells (HUVECs) and in non-small cell lung cancer (NSCLC) cell lines (A549 and H1299) by suppressing the expression of Cdk4 and cyclin D; hence, the cell cycle is halted [ 51 , 52 ]. It suppresses the expression and activity of MMPs (MMP-2) to prevent cell migration and invasion, which can also be prevented by inhibiting VEGF-A [ 51 ].…”

“…It suppresses the expression and activity of MMPs (MMP-2) to prevent cell migration and invasion, which can also be prevented by inhibiting VEGF-A [ 51 ]. In addition, marmesin significantly inhibits the VEGF-A-induced phosphorylation of FAK, Src, ERK, Akt, p70 S6K and MEK, and expression of cellular signaling molecules including vascular endothelial growth factor receptor-2 (VEGFR-2), human epidermal growth factor receptor 2 (HER2/neu), integrin β1 and integrin-linked kinase (ILK), which are closely associated with angiogenesis and cancer progression [ 51 , 52 ].…”