Morphological and immunocytochemical effects of dihydroartemisinin on differentiating NB2a neuroblastoma cells.
The toxicity caused by the artemisinin derivative dihydroartemisinin in differentiated NB2a neuroblastoma cells was studied by transmission and scanning electron microscopy, Western blotting and immunocytochemistry. Western blotting with monoclonal antibodies failed to detect any specific changes in the cell cytoskeleton, nor were any changes detected by immunocytochemistry. This was consistent with electron microscopy of surviving cell neurites. Transmission electron microscopy revealed that dihydroartemisinin damaged NB2a cell mitochondrial cristae and endoplasmic reticulum. Scanning electron microscopy revealed that dihydroartemisinin depleted the filopodia-like processes projecting from the surface of the cell body and neurites. Some, or all, of these drug-induced changes in differentiating NB2a cells may have a role in the neurotoxicity of artemisinin derivatives.
Fishwick
J
J
Department of Pharmacology and Therapeutics, University of Liverpool, UK.
Edwards
G
G
Ward
S A
SA
McLean
W G
WG
D000818:Animals; D000962:Antimalarials / Q000633:toxicity*; D037621:Artemisinins; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000032:analysis*; D005455:Fluorescent Antibody Technique; D051379:Mice; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D008868:Microtubule Proteins / Q000032:analysis; D009419:Nerve Tissue Proteins / Q000032:analysis*; D009447:Neuroblastoma / Q000473:pathology; D016900:Neurofilament Proteins / Q000032:analysis; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D012717:Sesquiterpenes / Q000633:toxicity*; D013049:Spectrin / Q000032:analysis
D000962:Antimalarials; D037621:Artemisinins; D003598:Cytoskeletal Proteins; D008868:Microtubule Proteins; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D012717:Sesquiterpenes; D013049:Spectrin; C039060:artenimol