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 language | English |
|---|---|
| Pages (from-to) | 1945-1958 |
| Number of pages | 14 |
| Journal | Current Pharmaceutical Design |
| Volume | 8 |
| Issue number | 22 |
| DOIs | |
| Publication status | Published - 2002 |
| Externally published | Yes |
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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 journal › Review article
}
TY - JOUR
T1 - Inhibition of NF-κB and proteasome activity in tumors
T2 - Can we improve the therapeutic potential of topoisomerase I and topoisomerase II poisons
AU - Ganapathi, Ram
AU - Vaziri, Susan A J
AU - Tabata, Masahiro
AU - Takigawa, Nagio
AU - Grabowski, Dale R.
AU - Bukowski, Ronald M.
AU - Ganapathi, Mahrukh K.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0036025366&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036025366&partnerID=8YFLogxK
U2 - 10.2174/1381612023393549
DO - 10.2174/1381612023393549
M3 - Review article
C2 - 12171521
AN - SCOPUS:0036025366
VL - 8
SP - 1945
EP - 1958
JO - Current Pharmaceutical Design
JF - Current Pharmaceutical Design
SN - 1381-6128
IS - 22
ER -