Administration of I[kappa]B-kinase inhibitor PS1145 enhances apoptosis in DMBA-induced tumor in male Wistar rats

Nuclear factor kappa-B (NF-[kappa]B), a key anti-apoptotic factor, plays a critical role in tumor cell growth, metastasis, and angiogenesis. The transcriptional activity of NF-[kappa]B is normally suppressed in the cytoplasm due to its association with a natural inhibitor molecule I[kappa]B. Phosphorylation of the I[kappa]B at Ser 32 and Ser 36 by the I[kappa]B kinase complex (IKK) marks the degradation of the molecule by 26S proteasome. As NF-[kappa]B is constitutively activated in most of the tumor cells, inhibition of the activities of IKK may significantly sensitize the tumor cells to apoptosis. In the present study, we investigated the effect of I[kappa]B kinase-specific blocker PS1145 on DMBA-induced skin tumor of male Wistar rats. We examined the apoptotic effect of PS1145 on DMBA-induced tumor by various histopathological and molecular techniques. Our results demonstrate the significant expression of major pro-apoptotic genes like caspases 2, 3, 8, 9, and p53 in PS1145-treated tumor bearing group at mRNA levels as well as significant (P