title: Polyphenolic flavonoids differ in their antiapoptotic efficacy in hydrogen peroxide-treated human vascular endothelial cells.
abstract: Oxidative injury induces cellular and nuclear damage that leads to apoptotic cell death. Agents or antioxidants that can inhibit production of reactive oxygen species can prevent apoptosis. We tested the hypothesis that flavonoids can inhibit H(2)O(2)-induced apoptosis in human umbilical vein endothelial cells. A 30-min pulse treatment with 0.25 mmol/L H(2)O(2) decreased endothelial cell viability within 24 h by approximately 40% (P < 0.05) with distinct nuclear condensation and DNA fragmentation. In the H(2)O(2) apoptosis model, the addition of 50 micro mol/L of the flavanol (-)epigallocatechin gallate and the flavonol quercetin, which have in vitro radical scavenging activity, partially (P < 0.05) restored cell viability with a reduction in H(2)O(2)-induced apoptotic DNA damage. In contrast, the flavones, luteolin and apigenin, at the nontoxic dose of 50 micro mol/L, intensified cell loss (P < 0.05) after exposure to H(2)O(2) and did not protect cells from oxidant-induced apoptosis. The flavanones, hesperidin and naringin, did not have cytoprotective effects. The antioxidants, (-)epigallocatechin gallate and quercetin, inhibited endothelial apoptosis, enhanced the expression of bcl-2 protein and inhibited the expression of bax protein and the cleavage and activation of caspase-3. Therefore, flavanols and flavonols, in particular (-)epigallocatechin gallate and quercetin, qualify as potent antioxidants and are effective in preventing endothelial apoptosis caused by oxidants, suggesting that flavonoids have differential antiapoptotic efficacies. The antiapoptotic activity of flavonoids appears to be mediated at the mitochondrial bcl-2 and bax gene level.
authors.affiliation: Division of Life Sciences and Silver Biotechnology Research Center, Hallym University, Chuncheon, Korea.
authors.forename: Yean-Jung
authors.initials: YJ
authors.lastname: Choi
authors.forename: Jung-Sook
authors.initials: JS
authors.lastname: Kang
authors.forename: Jung Han Yoon
authors.initials: JH
authors.lastname: Park
authors.forename: Yong-Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Jung-Suk
authors.initials: JS
authors.lastname: Choi
authors.forename: Young-Hee
authors.initials: YH
authors.lastname: Kang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D004587:Electrophoresis, Agar Gel; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004789:Enzyme Activation; D005419:Flavonoids / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D018384:Oxidative Stress; D010636:Phenols / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D005419:Flavonoids; D016166:Free Radical Scavengers; D010636:Phenols; D011108:Polymers; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D006861:Hydrogen Peroxide; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases