Suppression of Carnosine on Adhesion and Extravasation of Human Colorectal Cancer Cells

Abstract

Aim: To investigate the effect of carnosine, an active compound of dietary beef, fish and chicken, on the regulation of cell adhesion and extravasation during metastasis.

Materials and methods: Cell adhesion and extravasation abilities, and related regulating molecular mechanisms were analyzed in human colorectal cancer cells (HCT-116) and human umbilical vein cells (EA.hy926).

Results: Carnosine reduced the ability of HCT-116 cells to adhere to EA.hy926 cells. The expression levels of integrin-β1 in HCT-116 cells, as well as of intercellular adhesion molecule-1 and E-selectin in EA.hy926 cells, were reduced after carnosine treatment. After EA.hy926 cells were treated with carnosine, phosphorylation of vascular endothelia-cadherin (VE-cadherin), protein levels of Ras homologous (RHO) and RHO-associated coiled-coil containing protein kinase, and levels of reactive oxygen species were reduced. After treating EA.hy926 cells with carnosine, phosphorylation of inhibitor of kappa B (IκB) and DNA binding activity of nuclear factor-κB (NF-κB) were reduced.

Conclusion: Carnosine inhibits metastatic cell adhesion and extravasation by suppressing NF-κB signaling activation.

Keywords: Carnosine; NF-κB signaling pathway; cell adhesion; extravasation; permeability.