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 microM) and EA (100 and 200 microM) caused no change in externalization of PS, whereas FA (100 and 200 microM) 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 from 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 microM respectively. Although, the phenolics significantly inhibited DNA damage and lipid peroxidation, they could not alter the Bcl-2 expression in PBMCs. In conclusion, the anti-apoptotic effect of EA, CA and FA in PBMCs seems to be through the Bcl-2 independent mechanism.
Khanduja
Krishan Lal
KL
Department of Biophysics, Postgraduate Institute of Medical Education and Research, Chandigarh-160012, India. KlKhanduja@rediffmail.com
Avti
Pramod Kumar
PK
Kumar
Surender
S
Mittal
Nidhi
N
Sohi
Kiranjit Kaur
KK
Pathak
Chander Mohan
CM
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001713:Biphenyl Compounds; D002109:Caffeic Acids / Q000494:pharmacology*; D003373:Coumaric Acids / Q000494:pharmacology*; D004610:Ellagic Acid / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology; D010851:Picrates / Q000494:pharmacology; D059808:Polyphenols; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*
D000975:Antioxidants; D001713:Biphenyl Compounds; D002109:Caffeic Acids; D003373:Coumaric Acids; D005419:Flavonoids; D010636:Phenols; D010851:Picrates; D059808:Polyphenols; D019253:Proto-Oncogene Proteins c-bcl-2; D004610:Ellagic Acid; C004999:ferulic acid; D006861:Hydrogen Peroxide; C004931:1,1-diphenyl-2-picrylhydrazyl; C040048:caffeic acid