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

Anticancer Res. 2019 Nov;39(11):6135-6144. doi: 10.21873/anticanres.13821.


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.

MeSH terms

  • Apoptosis / drug effects
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carnosine / pharmacology*
  • Cell Adhesion / drug effects*
  • Cell Proliferation / drug effects
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Tumor Cells, Cultured


  • Biomarkers, Tumor
  • NF-kappa B
  • Carnosine