Ginkgo biloba extract regulates differentially the cell death induced by hydrogen peroxide and simvastatin.
Several human diseases have been associated with the overproduction of reactive oxygen species (ROS) and subsequently various antioxidants emerged as potential therapeutic agents that scavenge ROS. As an oxidative stress model of human disease, we used hydrogen peroxide (H2O2) to study effect of ROS on C6 glioma cells as a surrogate for astrocytes. H2O2 induced dose- and time-dependent apoptotic cell death which was preceded by growth arrest, and transiently activated the signalling proteins ATF-2, ERK1/2 and AKT in C6 glioma cells. While several antioxidants failed to block H2O2-induced apoptosis of these cells, Ginkgo biloba extract (EGb) totally prevented the cell death and growth inhibition induced by H2O2. Interestingly, EGb did not prevent the activation of ATF-2, ERK1/2 and AKT induced by H2O2 excluding the role of these factors in the pro-apoptotic effect of H2O2. We have previously shown that the lipid-lowering drug, simvastatin, causes apoptotic cell death in C6 glioma cells [Koyuturk M, Ersoz M, Altiok N. Simvastatin induces proliferation inhibition and apoptosis in C6 glioma cells via c-jun N-terminal kinase. Neurosci Lett 2004;370(2-3):212-7]. However, in parallel experiments with H2O2, EGb was unable to prevent cell death induced by simvastatin suggesting the involvement of separate signalling pathways between H2O2 and simvastatin. Thus, EGb and other plant flavonoids might have potential as protective agents against apoptosis through scavenging ROS upon cerebral or myocardial diseases associated with free radical generation.
Altiok
Nedret
N
Department of Pharmacology, Kadir Has University Faculty of Medicine, Vefa Bey Sokak No. 5, 80810 Gayrettepe, Istanbul, Turkey. naltiok@superonline.com
Ersoz
Melike
M
Karpuz
Vildan
V
Koyuturk
Meral
M
D051698:Activating Transcription Factor 2 / Q000502:physiology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000473:pathology; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D020441:Ginkgo biloba / Q000737:chemistry*; D005910:Glioma / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000633:toxicity*; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D009457:Neuroglia / Q000187:drug effects*; D016877:Oxidants / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D019821:Simvastatin / Q000633:toxicity*
C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016877:Oxidants; D010936:Plant Extracts; D019821:Simvastatin; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases