Specific IKKbeta inhibitor IV blocks Streptonigrin-induced NF-kappaB activity and potentiates its cytotoxic effect on cancer cells.

Department of Oncology, Wyeth Research, Pearl River, New York, USA.
Molecular Carcinogenesis (Impact Factor: 4.27). 06/2009; 48(8):678-84. DOI: 10.1002/mc.20550
Source: PubMed

ABSTRACT Many anticancer agents activate NF-kappaB, which plays an important role in the survival of cancer cells. Inhibition of NF-kappaB activity may therefore potentiate the efficacy of anticancer agents. We found that a previously used anticancer agent Streptonigrin (SN) was also a potent NF-kappaB inducer. Using a specific IKKbeta inhibitor IV (Podolin et al., J Pharmacol Exp Ther 2005; 312: 373-381), we revealed that the activation of NF-kappaB 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.

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