Nuclear factor-kappaB, induced in human carcinoma cell line A2780 by the new anthracycline men 10755, is devoid of transcriptional activity

Int J Cancer. 2002 Dec 10;102(5):476-82. doi: 10.1002/ijc.10745.


The new disaccharide anthracycline MEN 10755 induces activation of both NF-kappaB and p53 transcription factors in A2780 cells. Nevertheless, pharmacologic inhibition of NF-kappaB activation does not modify the sensitivity of A2780 cells to MEN 10755 treatment. To better characterize the role of NF-kappaB in MEN 10755-induced cytotoxicity, we analyzed the expression of a number of genes that are known to be regulated by NF-kappaB. None of these genes is modified by MEN 10755 treatment. On the contrary, our results suggest that the p53 DNA damage-responsive pathway is fully activated in A2780 cells, several genes controlled by p53 being up- or downregulated according to the described action of p53 on their promoters. Thus, in the A2780 cell line, the role of p53 in transducing the DNA-damage signal appears to be relevant, whereas NF-kappaB, although activated, appears to be nonfunctional. Other human carcinoma cell lines besides A2780 activate NF-kappaB DNA binding in response to MEN 10755 treatment, but again, this binding does not always lead to target gene activation. These results suggest that other factors, tumor type-specific and different from mere activation, could influence NF-kappaB transcriptional activity. Therefore, care should be taken when considering the pharmacologic inhibition of NF-kappaB as a means to improve anticancer therapy efficacy.

MeSH terms

  • Antibiotics, Antineoplastic / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Carcinoma / metabolism*
  • Disaccharides / pharmacology*
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / pharmacology*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Transcriptional Activation
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / metabolism


  • Antibiotics, Antineoplastic
  • Antineoplastic Agents
  • Disaccharides
  • NF-kappa B
  • Tumor Suppressor Protein p53
  • Doxorubicin
  • sabarubicin