Constitutive NF-kappa B activity influences basal apoptosis and radiosensitivity of head-and-neck carcinoma cell lines

Purpose: Nuclear factor-kappaB (NF-kappaB) has been implicated in anti-apop totic gene transactivation, according to its transcriptional activity. The present study was designed to investigate whether constitutive NF-kappaB ac tivity could modulate basal apoptosis and intrinsic radiosensitivity of KB, head-and-neck carcinoma cell line and KB3 subline. The KB3 subline was mor e radiosensitive (SF2 = 0.48, alpha = 0.064) than the radioresistant KB par ental cell line (SF2 = 0.80, alpha = 0.114). Methods and Materials: Constitutive NF-kappaB DNA-binding activity was dete rmined using electrophoretic mobility shift assay. Modulation of NF-kappaB activity was performed by exposing both cell lines to tumor necrosis factor a or dexamethasone. Apoptotic cell population was analyzed using flow cyto metry (annexin V/propidium iodide). Radiosensitivity was assessed from dete rmination of the surviving fraction at 2 Gy (SF2), and alpha and beta param eters were determined using the linear-quadratic model. Results: Constitutive NF-kappaB activity was found to be significantly lowe r in KB3 than in KB. KB cell line exposure to dexamethasone significantly d ecreased NF-kappaB DNA-binding activity and, consequently, enhanced baselin e apoptosis and radiosensitivity (alpha values: 0.114 vs. 0.052). Conversel y, exposure of KB3 cells to tumor necrosis factor a increased NF-kappaB DNA -binding activity and resulted in a significant decrease (50%) in rate of a poptosis and in radiosensitivity (SF2 values: 0.48 vs. 0.63). Conclusions: Modulation of NF-kappaB DNA-binding activity influences baseli ne apoptosis and intrinsic radiosensitivity. (C) 2001 Elsevier Science Inc.