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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.
AuthorsShang-Ming Chiou, Chiz-Hao Chiu, Su-Tso Yang, Jai-Sing Yang, Hui-Ying Huang, Chao-Lin Kuo, Po-Yuan Chen, Jing-Gung Chung
JournalNeurochemical research (Neurochem Res) Vol. 37 Issue 8 Pg. 1790-800 (Aug 2012) ISSN: 1573-6903 [Electronic] United States
PMID22592642 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anthraquinones
  • Apoptosis Inducing Factor
  • Reactive Oxygen Species
  • Cytochromes c
  • Endodeoxyribonucleases
  • endonuclease G
  • Caspases
  • Acetylcysteine
  • danthron
Topics
  • Acetylcysteine (pharmacology)
  • Animals
  • Anthraquinones (pharmacology)
  • Apoptosis (drug effects)
  • Apoptosis Inducing Factor (physiology)
  • Caspases (metabolism)
  • Cell Death (drug effects)
  • Cell Line, Tumor
  • Cytochromes c (metabolism)
  • Endodeoxyribonucleases (physiology)
  • Glioma (metabolism)
  • Membrane Potential, Mitochondrial (drug effects)
  • Mitochondria (drug effects, metabolism)
  • Rats
  • Reactive Oxygen Species (metabolism)
  • Signal Transduction (physiology)

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