NFxB Plays A Role in Basal Levels of ROS in HCT116 Cells

  • Ufuk Özer, PhD Dicle University
  • Karen W. Barbour, MSc University of South Carolina
Keywords: NFxB, colon cancer, 5-FU, NADPH oxidase, ROS

Abstract

Objectives: Nuclear factor kappa B (NFxB), a transcription factor, controls expression of many genes to stimulate immune response, cellular growth and differentiation. It has been usually known as an anti-apoptotic factor and its low levels contribute to cytotoxicity of thymidylate synthase (TS)-directed cancer therapy. As TS inhibitors, fluoropyrimidines, fluorouracil (5-FU) and its nucleoside analog 5’-fluoro-2’-deoxyuridine (FdUrd) have been utilized in colorectal cancer therapy. One of their cytotoxic impacts on the therapy is elevating ROS levels in order to promote oxidative cell death. To understand whether NFxB is involved in TS inhibitors-mediated ROS generation, we investigated the effects of NFxB on drug-mediated ROS accumulation in HCT116 cells.

Materials and Methods: ROS measurement in response to TS inhibitors was done in HCT116 cell line and its NFxB deficient, HCT116-dnIkBα, and its revertent, HCT116-dnIkBα-R cells. Cells were treated with drugs in order to determine NADPH oxidase (NOX) activity and mRNA expression of p67phox.

Results: Loss of NFxB did not alter increase in ROS formation mediated by TS inhibitors and drug-induced mRNA expression of p67phox and NOX activity. Basal levels of ROS and p67phox mRNA were increased by NFxB deficiency.

Conclusion: Findings show that loss of NFxB has no effects on drug-induced ROS, p67phox mRNA expression and NOX activity. However, we have determined that NFxB is an important suppressor for basal ROS formation in correlation with the induction of p67phox mRNA.

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Published
2016-10-20
How to Cite
Özer, U., & Barbour, K. W. (2016). NFxB Plays A Role in Basal Levels of ROS in HCT116 Cells. Acta Medica, 47(3), 87-92. Retrieved from https://actamedica.org/index.php/actamedica/article/view/29
Section
Original Article