Role of PI3-kinase/Akt pathway in the activation of etoposide-induced NF-κB transcription factor

NF-kappa B is a transcription factor involved in the innate immunity against bacterial infection and inflammation. It is also known to render cells resistant to the apoptosis caused by some anticancer drugs. Such a chemoresistance of cancer cells may be related to the activation of NF-kappa B transcription factor; however, the mechanism of activation is not well understood. Here, we demonstrate that a chemotherapeutic agent, etoposide, independently stimulates the I kappa B alpha degradation pathway and PI3-kinase/Akt signaling pathway: The classical I kappa B alpha degradation pathway leads to the nuclear translocation and DNA binding of p65 subunit through IKK beta kinase, whereas the PI3-kinase/Akt pathway plays a distinct role In activating this transcription factor. The PI3-kinase/Akt pathway acts on the p50 subunit of the NF-kappa B transcription factor and enhances the DNA binding affinity of the p50 protein. It may also explain the role of the PI3-kinase/Akt pathway in the anti-apoptotic function of NF-KB during chemoresistance of cancer cells.