Nuclear factor-kappa B, cancer, and apoptosis

The rule of nuclear factor (NF)-kappa B in the regulation of apoptosis in n ormal and cancer cells has been extensively studied in recent years. Consti tutive NF-kappa B activity in B lymphocytes as well as in Hodgkin's disease and breast cancer cells protects these cells against apoptosis. It has als o been reported that NF-kappa B activation by tumor necrosis factor (TNF)-a lpha, chemotherapeutic drugs, or ionizing radiations can protect several ce ll types against apoptosis, suggesting that NF-kappa B could participate in resistance to cancer treatment. These observations were explained by the r egulation of antiapoptotic gene expression by NF-kappa B. However, in our e xperience, inhibition of NF-kappa B activity in several cancer cell lines h as a very variable effect on cell mortality, depending on the cell type, th e stimulus, and the level of NF-kappa B inhibition. Moreover, in some exper imental systems, NF-kappa B activation is required for the onset of apoptos is. Therefore, it is likely that the NF-kappa B antiapoptotic role in respo nse to chemotherapy is cell type- and signal-dependent and that the level o f NF-kappa B inhibition is important. These issues will have to be carefull y investigated before considering NF-kappa B as a target for genetic or pha rmacological anticancer therapies. BIOCHEM PHARMACOL 60;8:1085-1090, 2000. (C) 2000 Elsevier Science Inc.