Anti-apoptotic and Pro-inflammatory Signaling in Cancer Cells: Status and Modulation by Chemotherapeutic Drugs

The transcription factor nuclear factor kappa-B (NFkB) plays a pivotal role in the immune response but is also involved in cancer development and progression. In unstimulated cells NFkB is kept inactive in the cytoplasm by inhibitor of NFkB (IkB) proteins. Dysregulation of the pathway or activation of NFkB by chemotherapeutic agents may lead to cancer progression or drug resistance. The NFkB activation status was investigated in human lung cancer, pancreatic cancer, and hematopoietic cancer cell lines. Additionally, the potential of cytotoxic drugs in activating the NFkB signaling pathway was analyzed. Furthermore, the influence of histone deacetylase inhibitors (HDIs) on the NFkB pathway in human non-small cell lung cancer (NSCLC) cell lines was investigated. Incubation of NSCLC cells with HDIs reduced the responsiveness of NFkB to tumor necrosis factor-alpha (TNF-a). It was shown that this reduction was due to drastic downregulation of TNF-receptor 1 by HDIs. This effect of HDIs could also be shown for other tumor entities and normal cell lines. This book is of particular interest for students, scientists, and professionals working on NFkB and/or HDIs.