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

Abstract

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.

• Authors: Grazia Camarda, Monica Binaschi, Carlo A Maggi, Cristina Goso
• Journal: International journal of cancer (Int J Cancer) Vol. 102 Issue 5 Pg. 476-82 (Dec 10 2002) ISSN: 0020-7136 [Print] United States
• PMID: 12432549 (Publication Type: Journal Article)
• Copyright: Copyright 2002 Wiley-Liss, Inc.

Chemical References

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

Topics

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