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RETRACTED ARTICLE

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Cell Death Differ. 2007 Jan;14(1):158-70. Epub 2006 Apr 28.

Inhibition of RelA phosphorylation sensitizes apoptosis in constitutive NF-kappaB-expressing and chemoresistant cells.

Author information

1
Laboratory of Immunology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India. manna@cdfd.org.in

Erratum in

  • Cell Death Differ. 2012 Sep;19(9):1572.

Abstract

The compound 5-(4-methoxyarylimino)-2-N-(3,4-dichlorophenyl)-3-oxo-1,2,4-thiadiazolidine (P(3)-25) is known to possess anti-bacterial, anti-fungal, anti-tubercular, and local anesthetic activities. We studied the anti-tumorigenic activity of P(3)-25 and the role of nuclear transcription factor kappaB (NF-kappaB) in this process. In constitutive NF-kappaB-expressing cells, treatment with P(3)-25 inhibited the expression of NF-kappaB-dependent reporter gene, adhesion molecules, and cyclooxygenase. It downregulated phosphorylation of p65 by inhibiting upstream kinases, such as protein kinase A and casein kinase II, but did not alter NF-kappaB DNA-binding activity. Alone, P(3)-25 induced apoptosis in NF-kappaB-expressing and doxorubicin-resistant breast cancer cells, and in the presence of other chemotherapeutic agents, it potentiated apoptosis. Overall, our results suggest that P(3)-25 exerts antitumorigenic activity by inhibiting phosphorylation of p65, the transcriptionally active subunit of NF-kappaB by inhibiting its upstream kinases, and potentiates apoptosis mediated by chemotherapeutic agents. These results suggest novel approaches for designing of anticancer drugs for combination chemotherapy.

PMID:
16645640
DOI:
10.1038/sj.cdd.4401929
[Indexed for MEDLINE]
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