Anti-apoptotic activity of caffeic acid, ellagic acid and ferulic acid in normal human peripheral. blood mononuclear cells: A Bcl-2 independent mechanism

Polyphenols have been shown to induce apoptosis in a variety of tumor cells including leukemia both in vitro and in vivo. However, their action on normal human peripheral blood mononuclear cells (PBMCs) during oxidative stress remains to be explored. In this study, we have evaluated the anti-apoptotic and radical scavenging activities of dietary phenolics, namely caffeic acid (CA), ellagic acid (EA) and ferulic acid (FA). H2O2-induced apoptosis in normal human PBMCs was assayed by phosphotidylserine externalization, nucleosomal damage and DNA fragmentation. Incubation of PBMCs with 5 mM H2O2 led to increased Annexin-V binding to externalized phosphatidyl serine (PS), an event of pre-apoptotic stage of the cell. Peripheral blood mononuclear cells pretreated with phenolics could resist H2O2-induced apoptotic damage. Caffeic acid (60 and 120 mu M) and EA (100 and 200 mu M) caused no change in externalization of PS, whereas FA (100 and 200 mu M) increased externalization of PS in PBMCs treated with H2O2. The effects of phenolics were abolished to a large extent by culturing the PBMCs for 24 h after washing the phenolics front the medium. Inhibitory activities of these phenolics on lipid peroxidation were in the order of EA < CA < FA. DPPH-scavenging activities of EA, CA and FA were found to be 31.2 +/- 1.36, 50 +/- 1.86 and 73.0 +/- 1.58 mu M respectively. Although, the phenolics significantly inhibited DNA damage and lipid peroxidation, they could not alter the Bcl-2 expression in PBMCs. fit conclusion, the anti-apoptotic effect of EA, CA and FA in PBMCs seems to be through the Bcl-2 independent mechanism. (c) 2005 Elsevier B.V. All rights reserved.