Differential regulation of NF-kappaB activation and function by topoisomerase II inhibitors.

BMC Cancer
Kirsteen J CampbellNeil D Perkins

Abstract

While many common chemotherapeutic drugs and other inducers of DNA-damage result in both NF-kappaB nuclear translocation and DNA-binding, we have previously observed that, depending on the precise stimulus, there is great diversity of the function of NF-kappaB. In particular, we found that treatment of U-2 OS osteosarcoma cells with the anthracycine daunorubicin or with ultraviolet (UV-C) light resulted in a form of NF-kappaB that repressed rather than induced NF-kappaB reporter plasmids and the expression of specific anti-apoptotic genes. Anthracyclines such as daunorubicin can induce DNA-damage though inhibiting topoisomerase II, intercalating with DNA and undergoing redox cycling to produce oxygen free radicals. In this study we have investigated other anthracyclines, doxorubicin and aclarubicin, as well as the anthracenedione mitoxantrone together with the topoisomerase II inhibitor ICRF-193, which all possess differing characteristics, to determine which of these features is specifically required to induce both NF-kappaB DNA-binding and transcriptional repression in U-2 OS cells. The use of mitoxantrone, which does not undergo redox cycling, and the reducing agent epigallocatechingallate (EGCG) demonstrated that oxygen fre...Continue Reading

References

Jan 1, 1985·Investigational New Drugs·R J White, F E Durr
Jan 1, 1989·Free Radical Biology & Medicine·I A ClarkW B Cowden
Jun 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·J H Doroshow
Mar 1, 1994·Proceedings of the National Academy of Sciences of the United States of America·J RocaJ C Wang
Sep 28, 1998·Biochimica Et Biophysica Acta·D A Burden, N Osheroff
Sep 29, 2000·Biochemical Pharmacology·S Schoonbroodt, J Piette
Sep 29, 2001·The Journal of Biological Chemistry·K C HuangR M Snapka
Jul 4, 2003·The EMBO Journal·Makio HayakawaKiyomi Kikugawa
Jul 31, 2003·Pharmacology & Therapeutics·Annette K LarsenAndrzej Skladanowski
Mar 27, 2004·Molecular Pharmacology·Jennifer D BilyeuMarcello Arsura
Apr 1, 2004·Molecular Cell·Kirsteen J CampbellNeil D Perkins
Apr 23, 2004·Trends in Cell Biology·Neil D Perkins
May 5, 2004·The Journal of Biological Chemistry·Vibe H OestergaardAnni H Andersen
Jun 4, 2004·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Ashok KumarBharat B Aggarwal
Jun 11, 2004·Cell Cycle·Kirsteen J Campbell, Neil D Perkins
Sep 17, 2004·Genes & Development·Matthew S Hayden, Sankar Ghosh
Dec 13, 2005·Biochemical Pharmacology·Saibal BiswasIrfan Rahman
Apr 22, 2006·Biochemical Society Symposium·Kirsteen J Campbell, Neil D Perkins

❮ Previous
Next ❯

Citations

Mar 13, 2012·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Abdullah OnulJames A Radosevich
Jan 20, 2012·Nature Reviews. Cancer·Neil D Perkins
Dec 2, 2008·Nature Reviews. Drug Discovery·Anwesha DeyDavid P Lane
Jul 7, 2011·Molecular Cancer Research : MCR·Irene RizRobert G Hawley
Mar 10, 2012·PloS One·Paolo TieriClaudio Franceschi
Dec 17, 2008·Journal of Experimental & Clinical Cancer Research : CR·Adrien DaigelerAnsgar M Chromik
Aug 30, 2011·Biochemical Pharmacology·Hélène SabatelYvette Habraken
Dec 10, 2008·International Journal of Cancer. Journal International Du Cancer·Johannes U AmmannSimone Fulda
Sep 4, 2009·Journal of Cellular and Molecular Medicine·Sabine KarlSimone Fulda
Mar 1, 2012·Expert Review of Molecular Diagnostics·Yu-Chang LiuJeng-Jong Hwang
Sep 13, 2006·Biochemical Pharmacology·Yvette Habraken, Jacques Piette
Aug 17, 2010·Biochimica Et Biophysica Acta·Sunil Kumar MaloniaSamit Chattopadhyay

❮ Previous
Next ❯

Methods Mentioned

BETA
ubiquitination
nuclear translocation
PCR
electrophoretic mobility shift

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.