Cyclooxygenase-2 Induction by Amino Acid Deprivation Requires p38 Mitogen-Activated Protein Kinase in Human Glioma Cells

ABSTRACT

Glioblastomas (GBMs) are malignant brain tumors that can outstrip nutrient supplies due to rapid growth. Cyclooxygenase-2 (COX-2) has been linked to GBMs and may contribute to their aggressive phenotypes. Amino acid starvation results in COX-2 mRNA and protein induction in multiple human glioma cell lines in a process requiring p38 mitogen-activated protein kinase (p38-MAPK) and the Sp1 transcription factor. Increased vascular endothelial growth factor expression results from starvation-dependent COX-2 induction. These data suggest that COX-2 induction with amino acid deprivation may be a part of the adaptation of glioma cells to these conditions, and potentially alter cellular response to anti-neoplastic therapy.

KEYWORDS:

• Glioblastomas
• amino acid deprivation
• COX-2
• p38-MAPK
• VEGF

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

Funding

This work is supported in part by grant (to Hui-Kuo G. Shu) from the Southeast Brain Tumor Foundation and fellowship (to Zhiwen Li) from the Youth Foundation (to Jilin University) of Health and Family Planning Commission of Jilin Province (3D5161453428). A Cancer Center grant (to Emory University) from the National Cancer Institute (P30-CA138292) also provided partial support for this work.