Modulation of ceramide-induced NF-kappa B binding activity and apoptotic response by caffeic acid in U937 cells: Comparison with other antioxidants

Ceramide acts as second messenger in the signal transduction triggered by a variety of stress stimuli and extracellular agents. Stress response throug h ceramide is involved in the development of many human diseases, such as a therosclerosis, inflammation, neurodegenerative disorders, and acquired imm unodeficiency syndrome. Dietary polyphenols have been reported to exert a b eneficial effect on the onset and development of most of these human chroni c-degenerative pathologies. However, the mechanisms underlying this benefic ial effect an mostly not understood at the present. To investigate the abil ity of polyphenols in modulating fundamental cellular functions, we studied the effect of caffeic acid, a widespread phenolic acid largely present in human diet, in the modulation of ceramide-induced signal transduction pathw ay leading to apoptosis in U937 cells, in comparison with other established antioxidants of nutritional. interest (N-acetylcysteine, d-alpha -tocopher ol acetate and ascorbic acid). Our results indicate that caffeic acid effic iently inhibits both ceramide-induced NF-kappaB binding activity and apopto sis at mu molar concentration. Other antioxidants tested are totally ineffe ctive in inhibiting apoptosis, although affecting NF-kappaB activation. Caf feic acid was found to inhibit protein tyrosine kinase activity, suggesting that this mechanism can be on the basis of the inhibition of apoptosis. Ou r results suggest that dietary caffeic acid might modulate ceramide-induced signal transduction pathway and NF-kappaB activation through either antiox idant and nonantioxidant mechanisms. (C) 2001 Elsevier Science Inc.