High constitutive level of NF-kappaB is crucial for viability of adenocarcinoma cells.
Most of cells exhibit low nuclear level of NF-kappaB. However, in some cell lines and tissues aberrantly activated NF-kappaB is playing an important role in cell motility, growth control and survival. Here we describe the result of decrease of constitutive NF-kappaB level in different adenocarcinoma cell lines. Treatment of mouse adenocarcinoma cell line CSML-100 with both synthetic (TPCK or PDTC) or natural (I(kappaB)-alpha) NF-kappaB inhibitors caused apoptotic death. Low doses of TPCK were harmless for CSML100 cells but sensitized them to TNF-induced apoptosis. Death of CSML100 cells in the presence of high concentration TPCK was not accompanied with significant changes in c-myc activity but strongly correlated with rapid decrease in p53 level. Thus, mutual behavior p53 and NF-kappaB represented a unique feature of TPCK-induced apoptosis in CSML-100 adenocarcinoma cells.
Smirnov
A S
AS
Group of Transcriptional Control and Oncogenesis, Institute of Gene Biology, Russian Academy of Sciences, Vavilova 34/5, 117334 Moscow, Russia.
Ruzov
A S
AS
Budanov
A V
AV
Prokhortchouk
A V
AV
Ivanov
A V
AV
Prokhortchouk
E B
EB
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005434:Flow Cytometry; D015726:Giant Cells / Q000378:metabolism / Q000473:pathology; D020672:I-kappa B Proteins; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000737:chemistry / Q000378:metabolism*; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D021122:Protein Subunits; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D013859:Thiocarbamates / Q000494:pharmacology; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D004268:DNA-Binding Proteins; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D021122:Protein Subunits; D016271:Proto-Oncogene Proteins c-myc; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; C066229:prolinedithiocarbamate; D000072000:NF-KappaB Inhibitor alpha; D014108:Tosylphenylalanyl Chloromethyl Ketone; D011392:Proline