Prostaglandin A1 Inhibits Stress-Induced NF-κB Activation and Reverses Resistance to Topoisomerase II Inhibitors

$79.00 plus tax (Refund Policy)

Buy Article:

Abstract:

Stress conditions associated with solid tumors lead to the formation of heterogeneous tumor cell subpopulations and insensitivity to cancer chemotherapeutics. In this report, we show that EMT6 mouse mammary tumor cells treated with the chemical stress, brefeldin A (BFA), or the physiological stress, hypoxia, develop resistance to the topoisomerase II (topoII) inhibitors teniposide and etoposide. BFA and hypoxia treatment did not alter intracellular drug concentrations, topoII protein levels, or inhibit topoII activity. BFA and hypoxia did cause the activation of the nuclear transcription factor NF-κB. We demonstrate that pretreatment with the synthetic cyclopentenone prostaglandin A1 (PGA1) inhibits stress-induced NF-κB activation and reverses BFA- and hypoxia-induced resistance. The reversal of BFA-induced resistance can occur when PGA1 is administered either before or several hours after the induction of stress. Taken together, these data support the involvement of NF-κB in stress-induced drug resistance, show that pharmacologic inhibitors of NF-κB can disrupt the biological consequences of stress, and imply that inhibitors of NF-κB may be useful agents to enhance the clinical efficacy of topoII-directed chemotherapeutics.

Keywords: Drug resistance; Etoposide; Key words: Nuclear factor-κB; Prostaglandin A1; Stress

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/096504001108747846

Affiliations: Department of Pharmacology, The George Washington University Medical Center, Washington, DC 20037

Publication date: January 1, 2001

More about this publication?
  • Formerly: Oncology Research Incorporating Anti-Cancer Drug Design
    Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.
Related content

Tools

Favourites

Share Content

Access Key

Free Content
Free content
New Content
New content
Open Access Content
Open access content
Subscribed Content
Subscribed content
Free Trial Content
Free trial content
Cookie Policy
X
Cookie Policy
ingentaconnect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more