High constitutive level of NF-kappaB is crucial for viability of adenocarcinoma cells

A S Smirnov; A S Ruzov; A V Budanov; A V Prokhortchouk; A V Ivanov; E B Prokhortchouk

doi:10.1038/sj.cdd.4400853

High constitutive level of NF-kappaB is crucial for viability of adenocarcinoma cells

Cell Death Differ. 2001 Jun;8(6):621-30. doi: 10.1038/sj.cdd.4400853.

Authors

A S Smirnov¹, A S Ruzov, A V Budanov, A V Prokhortchouk, A V Ivanov, E B Prokhortchouk

Affiliation

¹ Group of Transcriptional Control and Oncogenesis, Institute of Gene Biology, Russian Academy of Sciences, Vavilova 34/5, 117334 Moscow, Russia.

PMID: 11536013
DOI: 10.1038/sj.cdd.4400853

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma / metabolism*
Adenocarcinoma / pathology*
Animals
Apoptosis / drug effects
Cell Nucleus / drug effects
Cell Nucleus / metabolism
Cell Nucleus / pathology
Cell Survival
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism
Dose-Response Relationship, Drug
Down-Regulation / drug effects
Flow Cytometry
Giant Cells / metabolism
Giant Cells / pathology
I-kappa B Proteins*
Mice
NF-KappaB Inhibitor alpha
NF-kappa B / chemistry
NF-kappa B / metabolism*
Proline / analogs & derivatives
Proline / pharmacology
Protein Binding / drug effects
Protein Subunits
Proto-Oncogene Proteins c-myc / metabolism
Thiocarbamates / pharmacology
Tosylphenylalanyl Chloromethyl Ketone / pharmacology
Transfection
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha / pharmacology
Tumor Suppressor Protein p53 / metabolism

Substances

DNA-Binding Proteins
I kappa B beta protein
I-kappa B Proteins
NF-kappa B
Nfkbia protein, mouse
Protein Subunits
Proto-Oncogene Proteins c-myc
Thiocarbamates
Tumor Necrosis Factor-alpha
Tumor Suppressor Protein p53
prolinedithiocarbamate
NF-KappaB Inhibitor alpha
Tosylphenylalanyl Chloromethyl Ketone
Proline