NF-kappaB is a transcriptional regulator that plays a key role in immunity, inflammation and programmed cell death. We generated a PC12 cell line termed PC12kappaBluc that contains an integrated NF-kappaB-responsive reporter gene to directly measure NF-kappaB activity. The "classical" activators of NF-kappaB, phorbol 12-O-tetradecanoate-13-acetate and tumor necrosis factor alpha, strongly induced NF-kappaB activity in PC12kappaBluc cells. Activation of NF-kappaB could be attenuated by preincubating the cells with the cAMP analogue dbcAMP or via expression of the superrepressor IkappaBalphaS32A/S36A. PC12kappaBluc cells were subjected to several apoptotic paradigms, including treatment with 6-hydroxydopamine, H2O2, K2Cr2O7, MnCl2, C2-ceramide or the cannabinoid receptor-1 agonist CP55,940. A simultaneous measurement of the NF-kappaB activity revealed that only administration of 6-hydroxydopamine or CP55,940 increased NF-kappaB activity. Using pharmacological and genetic strategies to attenuate NF-kappaB transcriptional activity, we demonstrate that the elevation of NF-kappaB activity by 6-hydroxydopamine and CP55,940 is not an integral part of the apoptotic signaling cascade in PC12 cells.