PURPOSE: 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 AND MATERIALS: 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.
PURPOSE: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 AND MATERIALS: 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.
Authors: Y Zhang; J Y Lang; L Liu; J Wang; G Feng; Y Jiang; Y L Deng; X J Wang; Y H Yang; T Z Dai; G Xie; J Pu; X B Du Journal: Med Oncol Date: 2010-05-25 Impact factor: 3.064
Authors: Bert H O'Neil; William K Funkhouser; Benjamin F Calvo; Michael O Meyers; Hong Jin Kim; Richard M Goldberg; Stephen A Bernard; Laura Caskey; Allison M Deal; Fred Wright; Albert S Baldwin; Joel E Tepper Journal: Int J Radiat Oncol Biol Phys Date: 2010-07-12 Impact factor: 7.038
Authors: Enn Seppet; Marju Gruno; Ants Peetsalu; Zemfira Gizatullina; Huu Phuc Nguyen; Stefan Vielhaber; Manfred H P Wussling; Sonata Trumbeckaite; Odeta Arandarcikaite; Doreen Jerzembeck; Maria Sonnabend; Katharina Jegorov; Stephan Zierz; Frank Striggow; Frank N Gellerich Journal: Int J Mol Sci Date: 2009-05-19 Impact factor: 6.208