被撤回的出版物: Inhibition of RelA phosphorylation sensitizes apoptosis in constitutive NF-kappaB-expressing and chemoresistant cells (Retracted article. See vol. 20, pg. 784, 2013)

The compound 5-(4-methoxyarylimino)-2-N-(3,4-dichlorophenyl)-3-oxo-1,2,4-thiadiazolidine (P-3-25) is known to possess antibacterial, 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-KB) in this process. In constitutive NF-KB-expressing cells, treatment with P-3-25 inhibited the expression of NF-KB-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-KB DNA-binding activity. Alone, P-3-25 induced apoptosis in NF-KB- 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-KB 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.