Nuclear factor-κB, cancer, and apoptosis

The role of nuclear factor (NF)-κB in the regulation of apoptosis in normal and cancer cells has been extensively studied in recent years. Constitutive NF-κB activity in B lymphocytes as well as in Hodgkin's disease and breast cancer cells protects these cells against apoptosis. It has also been reported that NF-κB activation by tumor necrosis factor (TNF)-α, chemotherapeutic drugs, or ionizing radiations can protect several cell types against apoptosis, suggesting that NF-κB could participate in resistance to cancer treatment. These observations were explained by the regulation of antiapoptotic gene expression by NF-κB. However, in our experience, inhibition of NF-κB activity in several cancer cell lines has a very variable effect on cell mortality, depending on the cell type, the stimulus, and the level of NF-κB inhibition. Moreover, in some experimental systems, NF-κB activation is required for the onset of apoptosis. Therefore, it is likely that the NF-κB antiapoptotic role in response to chemotherapy is cell type- and signal-dependent and that the level of NF-κB inhibition is important. These issues will have to be carefully investigated before considering NF-κB as a target for genetic or pharmacological anticancer therapies. (C) 2000 Elsevier Science Inc.