Matrine inhibits the adhesion and migration of BCG823 gastric cancer cells by affecting the structure and function of the vasodilator-stimulated phosphoprotein (VASP)

Abstract

Aim: Vasodilator-stimulated phosphoprotein (VASP) expression is upregulated in human cancers and correlates with more invasive advanced tumor stages. The aim of this study was to elucidate the mechanisms by which matrine, an alkaloid derived from Sophora species plants, acted on the VASP protein in human gastric cancer cells in vitro. Methods: VASP was expressed and purified. Intrinsic fluorescence spectroscopy was used to study the binding of matrine to VASP. CD spectroscopy was used to examine the changes in the VASP protein secondary structure. Human gastric carcinoma cell line BGC823 was tested. Scratch wound and cell adhesion assays were used to detect the cell migration and adhesion, respectively. Real-time PCR and Western blotting assays were used to measure mRNA and protein expression of VASP. Results: In the fluorescence assay, the dissociation constant for binding of matrine to VASP protein was 0.86 mmol/L, thus the direct binding between the two molecules was weak. However, matrine (50 μg/mL) caused obvious change in the secondary structure of VASP protein shown in CD spectrum. Treatments of BGC823 cells with matrine (50 μg/mL) significantly inhibited the cell migration and adhesion. The alkaloid changed the subcellular distribution of VASP and formation of actin stress fibers in BGC823 cells. The alkaloid caused small but statistically significant decreases in VASP protein expression and phosphorylation, but had no significant effect on VASP mRNA expression. Conclusion: Matrine modulates the structure, subcellular distribution, expression and phosphorylation of VASP in human gastric cancer cells, thus inhibiting the cancer cell adhesion and migration.

Tumor suppressor berberine binds VASP to inhibit cell migration in basal-like breast cancer

“…VASP protein was expressed in E. coli Rosetta by induction with 0.5 mM isopropyl-1-thio-β-D-galactopyranoside (IPTG) at 18°C for 16 h as previously described [51, 52]. The intrinsic fluorescence spectroscopy was used to investigate the interaction between berberine with VASP at 25°C by LS-55 luminescence spectrometer (Perkin-Elmer Life Sciences, Shelton, CT).…”

Matrine Directly Activates Extracellular Heat Shock Protein 90, Resulting in Axonal Growth and Functional Recovery in Spinal Cord Injured-Mice

“…In recent years, several basic studies showed direct binding proteins of matrine. Epidermal growth factor receptor (Wang et al, 2010 ), vasodilator-stimulated phosphoprotein (Zhang et al, 2013 ), and annexin A2 (Wang et al, 2017 ) were identified as the direct binding proteins of matrine in cancer cells, and matrine inhibited these protein-induced cell events. Cui et al showed that matrine bound to amyloid β peptide and receptor for advanced glycation end products, and the cell signaling stimulated by these proteins were inhibited by matrine in neuroblastoma cells (Cui et al, 2017 ).…”

Construction of Multiple Switchable Sensors and Logic Gates Based on Carboxylated Multi-Walled Carbon Nanotubes/Poly(N,N-Diethylacrylamide)

“…Matrine and sophoridine are quinolizidine alkaloids isolated from traditional Chinese medicine such as Sophora flavescens, Sophora subprostrata, or Sophora alopecuroides, which are tetracyclic quinolizine compounds with a molecular skeleton and can be regarded as a combination of two quinolizine rings [ 19 , 20 ]. In recent years, it has been discovered that the alkaloids of S. flavescens exhibit anti-arrhythmic, anti-inflammatory, anti-fibrosis, anti-tumor, and numerous other significant pharmacological activities, and various formulations have been widely used in clinical practice [ 21 , 22 , 23 , 24 ]. Therefore, in the present work, we used matrine and sophoridine as target drug molecule probes to study the switching properties of the binary carboxylated multi-walled carbon nanotubes/poly( N , N -diethylacrylamide) (c-MWCNTs/PDEA) film system.…”