Antiapoptotic effect of aminoguanidine on doxorubicin-induced apoptosis.
Doxorubicin (DOX) is a broad-spectrum anthracycline that has cardiotoxicity as a major side effect. Reactive oxygen species (ROS) and reactive nitrogen species generations have been proposed to be an important mechanism of DOX-induced cardiotoxicity and cardiomyocyte apoptosis, which may be mediated by p53 protein. Aminoguanidine (AG) is an effective antioxidant due to its free radical scavenger activity. A549 lung cell line was incubated with various concentrations of AG (100-1,000 μM) wit/without 0.25 μM DOX for 24 h. The expression of p53 and its transcriptional target p21 were analyzed by Western blot. Apoptosis was analyzed with Annexin V assay. JC1 and H2AX immunofluorescence were used to assess mitochondrial and nuclear DNA damage, respectively. This study demonstrated that AG has a dose-dependent antiapoptotic effect on DOX-induced apoptosis. Thus, these data further identify AG as a potential chemopreventive agent to reduce ROS and nitric oxide synthase damage generated by DOX.
Department of Toxicology, Faculty of Pharmacy, Hacettepe University, 06100, Sihhiye, Ankara, Turkey, sunaatasayar@hotmail.com.
Suna
S
Sabuncuoglu
D000970:Antineoplastic Agents / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000633:toxicity*; D006146:Guanidines / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000970:Antineoplastic Agents; D000975:Antioxidants; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004272:DNA, Mitochondrial; D006146:Guanidines; C468783:H2AX protein, human; D006657:Histones; D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; C004479:pimagedine