Differential oxidative response to fluoropyrimidines in colorectal cancer cell lines

Authors: UFUK ÖZER, KAREN WOOD BARBOUR

Abstract: Colorectal cancer (CRC) is the second most common human malignancy in women and the third in men, accounting for approximately 8% of cancer-related deaths and 1.3 million newly diagnosed cases annually worldwide. CRC cell lines differ in morphological features, growth rate, and their genetic alterations, implicating the extent of variability among the lines. The goal of the current study was to investigate the phenotypes of CRC lines related to NADPH oxidase (NOX) activity and expression of NOX2 subunits in response to fluoropyrimidines. NOX activity in response to 5'-fluoro-2'-deoxyuridine (FdUrd) and VAS2780 was measured in CRC cell lines. Cells were treated with FdUrd in order to determine apoptotic cell death and mRNA expressions of NOX2 cytoplasmic subunits. We find that both basal and drug-induced NOX activity differ in the lines. Similarly, drug-mediated apoptotic indices vary in the cell lines at basal levels. Among NOX1 and NOX2 subunits, only NOX2 accessory subunits, p67phox, p40phox, and p47phox, differ in the lines. Our results show that CRC cells have diverse oxidative background and their oxidative response to anticancer drugs vary, while they all exhibit increases in NOX activity.

Keywords: NADPH oxidase, fluoropyrimidines, oxidative stress, CRC cells

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