title: A comparative study of phytoestrogen action in mitigating apoptosis induced by oxidative stress.
abstract: The phytoestrogens kaempferol, genistein and genistin were characterized using in vitro assays utilizing iodoacetic acid (IAA)-induced oxidative stress and mitochondrial dysfunction. RGC-5 cells were treated with different concentrations of IAA, and phytoestrogens were administered along with IAA. IAA is cytotoxic to RGC-5 cells and induces the generation of reactive oxygen species (ROS) in vitro. Genistein rescued RGC-5 cells in the presence of IAA, however, it also increased caspase activation and did not inhibit the generation of ROS. Genistein increased phosphorylation of ribosomal s6 kinase (p90RSK), reduced phosphorylation of the ribosomal S6 protein, and had no effect on phosphorylation of protein kinase B (AKT). Kaempferol and genistin rescued RGC-5 cells from IAA-induced cell death, as well as reduced caspase activation and ROS generation. Kaempferol increased phosphorylation of AKT and MAP kinase (p44/42). Genistin reduced phosphorylation of p42 and p90RSK. Although these phytoestrogens are flavonoids and similar in structure, they exhibit different effects on cell signaling.
authors.affiliation: Cell Biology and Anatomy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
authors.forename: Amber J
authors.initials: AJ
authors.lastname: Ondricek
authors.forename: Abhishek K
authors.initials: AK
authors.lastname: Kashyap
authors.forename: Sanjay I
authors.initials: SI
authors.lastname: Thamake
authors.forename: Jamboor K
authors.initials: JK
authors.lastname: Vishwanatha
mesh_terms: D000818:Animals; D047310:Apigenin / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004355:Drug Stability; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D044948:Flavonols; D016166:Free Radical Scavengers / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D019807:Iodoacetic Acid / Q000494:pharmacology; D007529:Isoflavones / Q000494:pharmacology*; D044949:Kaempferols / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D048789:Phytoestrogens / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D005419:Flavonoids; D044948:Flavonols; D016166:Free Radical Scavengers; D007529:Isoflavones; D044949:Kaempferols; D016877:Oxidants; D048789:Phytoestrogens; D017382:Reactive Oxygen Species; C040641:genistin; D004958:Estradiol; C006552:kaempferol; D047310:Apigenin; D019833:Genistein; C505410:Casp3 protein, rat; D053148:Caspase 3; C017875:fisetin; D019807:Iodoacetic Acid