Constitutive NF-kappaB activity influences basal apoptosis and radiosensitivity of head-and-neck carcinoma cell lines.
OBJECTIVE
Nuclear factor-kappaB (NF-kappaB) has been implicated in anti-apoptotic gene transactivation, according to its transcriptional activity. The present study was designed to investigate whether constitutive NF-kappaB activity could modulate basal apoptosis and intrinsic radiosensitivity of KB head-and-neck carcinoma cell line and KB3 subline. The KB3 subline was more radiosensitive (SF2 = 0.48, alpha = 0.064) than the radioresistant KB parental cell line (SF2 = 0.80, alpha = 0.114).


METHODS
Constitutive NF-kappaB DNA-binding activity was determined using electrophoretic mobility shift assay. Modulation of NF-kappaB activity was performed by exposing both cell lines to tumor necrosis factor alpha or dexamethasone. Apoptotic cell population was analyzed using flow cytometry (annexin V/propidium iodide). Radiosensitivity was assessed from determination of the surviving fraction at 2 Gy (SF2), and alpha and beta parameters were determined using the linear-quadratic model.


RESULTS
Constitutive NF-kappaB activity was found to be significantly lower in KB3 than in KB. KB cell line exposure to dexamethasone significantly decreased NF-kappaB DNA-binding activity and, consequently, enhanced baseline apoptosis and radiosensitivity (alpha values: 0.114 vs. 0.052). Conversely, exposure of KB3 cells to tumor necrosis factor alpha increased NF-kappaB DNA-binding activity and resulted in a significant decrease (50%) in rate of apoptosis and in radiosensitivity (SF2 values: 0.48 vs. 0.63).


CONCLUSIONS
Modulation of NF-kappaB DNA-binding activity influences baseline apoptosis and intrinsic radiosensitivity.
Didelot
C
C
Laboratoire de Recherche en Oncologie, Centre Alexis Vautrin, Nancy, France.
Barberi-Heyob
M
M
Bianchi
A
A
Becuwe
P
P
Mirjolet
J F
JF
Dauça
M
M
Merlin
J L
JL
D017209:Apoptosis; D004247:DNA / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D016328:NF-kappa B / Q000502:physiology*; D011836:Radiation Tolerance; D014407:Tumor Cells, Cultured
D016328:NF-kappa B; D004247:DNA