Reactive oxygen species (ROS) reduce the expression of BRAK/CXCL14 in human head and neck squamous cell carcinoma cells

Abstract

The present study investigated the effects of oxidative stress induced by reactive oxygen species (ROS), such as hydrogen peroxide (H₂O₂) and hydroxyl radical (HO^•), on the expression of both BRAK , which is also known as non-ELR motif angiostatic CXC chemokine ligand 14 (CXCL14), in head and neck squamous cell carcinoma (HNSCC) cells. When HNSCC cells were cultured in the presence of ROS, the expression of BRAK was significantly decreased whereas that of IL-8 was increased. Interestingly, the effects on the expression of both genes in HNSCC cells were much greater with HO^▪ than with H₂O₂. The effects of ROS on both BRAK and IL-8 expression were attenuated by pre-treatment with N-acetyl-L-cysteine (NAC), epidermal growth factor receptor (EGFR), and mitogen-activated protein kinase (MAPK) inhibitors. These results indicate that oxidative stress induced by H₂O₂ or HO^• stimulates angiogenesis and tumuor progression by altering the gene expression of BRAK and IL-8 via the EGFR/MEK/ERK pathway in human HNSCC cells.

Keywords::

• Reactive oxygen species
• BRAK
• IL-8
• H₂O₂
• hydroxyl radical
• HNSCC cell

Declaration of interest: Supported by grants from High-Tech Research Center Project of Kanagawa Dental College, Yokosuka, Kanagawa, Japan and Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Science, and Culture to 16791169, 18890213, 21390543 and 19592371.