Inhibition of NF-κB and proteasome activity in tumors: Can we improve the therapeutic potential of topoisomerase I and topoisomerase II poisons

Ram Ganapathi, Susan A J Vaziri, Masahiro Tabata, Nagio Takigawa, Dale R. Grabowski, Ronald M. Bukowski, Mahrukh K. Ganapathi

Research output: Contribution to journalReview article

14 Citations (Scopus)

Abstract

Activation of signaling pathways following DNA damage induced by topoisomerase (topo) poisons can lead to cell death by apoptosis. NF-κB, a major regulator of the stress response and a negative regulator of apoptosis is often activated following treatment with topoisomerase poisons. Since activation of NF-κB is generally considered to relay an anti-apoptotic signal, inactivation of this signaling molecule is considered to represent an important strategy to improve therapeutic efficacy. Although this strategy seems to be effective in some model systems, our results in human non-small cell lung cancers differed. In this review we will discuss the role of NF-κB in mediating topoisomerase poison-induced DNA damage and apoptosis and the consequence of inhibiting its activity. Newer insights about the importance of proteasome inhibitors and anti-apoptotic genes in topoisomerase poison-induced signaling mechanisms leading to apoptosis will also be reviewed. The knowledge obtained from these studies may be useful for translation to a clinical setting for development of more effective therapeutic strategies.

Original languageEnglish
Pages (from-to)1945-1958
Number of pages14
JournalCurrent Pharmaceutical Design
Volume8
Issue number22
DOIs
Publication statusPublished - 2002
Externally publishedYes

Fingerprint

Type II DNA Topoisomerase
Type I DNA Topoisomerase
Poisons
Proteasome Endopeptidase Complex
Apoptosis
DNA Damage
Neoplasms
Proteasome Inhibitors
Therapeutics
Non-Small Cell Lung Carcinoma
Cell Death
Genes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Inhibition of NF-κB and proteasome activity in tumors : Can we improve the therapeutic potential of topoisomerase I and topoisomerase II poisons. / Ganapathi, Ram; Vaziri, Susan A J; Tabata, Masahiro; Takigawa, Nagio; Grabowski, Dale R.; Bukowski, Ronald M.; Ganapathi, Mahrukh K.

In: Current Pharmaceutical Design, Vol. 8, No. 22, 2002, p. 1945-1958.

Research output: Contribution to journalReview article

Ganapathi, Ram ; Vaziri, Susan A J ; Tabata, Masahiro ; Takigawa, Nagio ; Grabowski, Dale R. ; Bukowski, Ronald M. ; Ganapathi, Mahrukh K. / Inhibition of NF-κB and proteasome activity in tumors : Can we improve the therapeutic potential of topoisomerase I and topoisomerase II poisons. In: Current Pharmaceutical Design. 2002 ; Vol. 8, No. 22. pp. 1945-1958.
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