title: Danthron triggers ROS and mitochondria-mediated apoptotic death in C6 rat glioma cells through caspase cascades, apoptosis-inducing factor and endonuclease G multiple signaling.
abstract: This research focused on the induction of cytotoxic effects by danthron, a natural anthraquinone derivative on C6 rat glioma cells through exploring the means of cell death and the effects on mitochondrial function. We found that danthron decreased the percentage of viable C6 cells and induced cell morphological changes in a dose-and time-dependent manner. The morphological and nuclei changes (DAPI staining) in C6 cells were observed using a contrast-microscope and fluorescence microscopy, respectively. The results suggest that cell death of C6 cells which are induced by danthron is closely related to apoptotic death. Danthron decreased the level of mitochondrial membrane potential (ΔΨ( m )), stimulated the release of cytochrome c from mitochondria to cytosol and promoted the levels of caspase-9 and caspase-3, or induced the release of AIF and Endo G from mitochondria. Based on both observations, we suggest that the danthron-provoked apoptotic death of C6 cells is mediated through the mitochondria-dependent pathway. Furthermore, our results also indicated that danthron triggered apoptosis through reactive oxygen species (ROS) production which were increased after 1 h exposure of danthron, which was reversed by the ROS scavenger N-acetyl-L: -cysteine (NAC). As a consequence, danthron-mediated cell death of C6 cells via ROS production, mitochondrial transmembrane potential collapse and releases of cytochrome c, AIF and Endo G. Taken together, danthron was demonstrated to be effective in killing C6 rat glioma cells via the ROS-promoted and mitochondria-dependent apoptotic pathways.
authors.affiliation: Department of Functional Neurosurgery, Gamma Knife Center, China Medical University Hospital, Taichung 404, Taiwan.
authors.forename: Shang-Ming
authors.initials: SM
authors.lastname: Chiou
authors.forename: Chiz-Hao
authors.initials: CH
authors.lastname: Chiu
authors.forename: Su-Tso
authors.initials: ST
authors.lastname: Yang
authors.forename: Jai-Sing
authors.initials: JS
authors.lastname: Yang
authors.forename: Hui-Ying
authors.initials: HY
authors.lastname: Huang
authors.forename: Chao-Lin
authors.initials: CL
authors.lastname: Kuo
authors.forename: Po-Yuan
authors.initials: PY
authors.lastname: Chen
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000502:physiology*; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000502:physiology; D005910:Glioma / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D000880:Anthraquinones; D051033:Apoptosis Inducing Factor; D017382:Reactive Oxygen Species; D045304:Cytochromes c; D004706:Endodeoxyribonucleases; C052391:endonuclease G; D020169:Caspases; D000111:Acetylcysteine; C004315:danthron