Specific IKKβ inhibitor IV blocks streptonigrin-induced NF-κB activity and potentiates its cytotoxic effect on cancer cells
✍ Scribed by Maria Gavriil; Cheng-Chung Tsao; Sreekala Mandiyan; Kim Arndt; Robert Abraham; Yixian Zhang
- Book ID
- 102499303
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 276 KB
- Volume
- 48
- Category
- Article
- ISSN
- 0899-1987
- DOI
- 10.1002/mc.20550
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✦ Synopsis
Abstract
Many anticancer agents activate NF‐κB, which plays an important role in the survival of cancer cells. Inhibition of NF‐κB activity may therefore potentiate the efficacy of anticancer agents. We found that a previously used anticancer agent Streptonigrin (SN) was also a potent NF‐κB inducer. Using a specific IKKβ inhibitor IV (Podolin et al., J Pharmacol Exp Ther 2005; 312: 373–381), we revealed that the activation of NF‐κB was mediated through DNA damage‐induced activation of IKK complex. Furthermore, we demonstrated that SN‐induced DNA damage was unrelated to reactive oxygen species but to the hydroquinone form of SN converted by the NAD(P)H:quinine oxidoreductase (NQO1). The study suggests that the combination of SN with IKK inhibitor may improve efficacy over the use of single agent. © 2009 Wiley‐Liss, Inc.