Apoptosis induced neurotoxicity of Di-n-butyl-di-(4-chlorobenzohydroxamato) Tin (IV) via mitochondria-mediated pathway in PC12 cells.
Toxicol In Vitro
; 27(1): 92-102, 2013 Feb.
Article
en En
| MEDLINE
| ID: mdl-23041257
ABSTRACT
The severe toxicity of antitumor organotin (IV) compounds limits their application in clinic, however, the toxic mechanism is still unclear. Di-n-butyl-di-(4-chlorobenzohydroxamato) Tin (IV) (DBDCT), an antitumor agent with high activity and obvious neurotoxicity was chosen as a typical diorganotin (IV) compound to investigate its neurotoxic mechanism using PC12 cells and comprehensive methods. Treatment with DBDCT resulted in a dose- and time-dependent growth inhibition of PC12 cells. The changes in cell morphology were observed using light microscopy, fluorescence microscopy and transmission electron microscopy. PC12 cell apoptosis induced by DBDCT was confirmed by annexin V/propidium iodide staining, and characterized by cleavage of caspase-9 and caspase-3 proteins. DBDCT induced the release of cytochrome c from the mitochondria to the cytosol and the generation of reactive oxygen species. DBDCT up-regulated the expression of Bax, down-regulated the expression of Bcl-2, and significantly increased the ratio of Bax/Bcl-2. DBDCT also caused the phosphorylation of JNK and p38(MAPK). In rats exposed to DBDCT, apoptosis was also observed in brain, as shown by the detection of cleaved caspase-9 and caspase-3 proteins and increased TUNEL positive staining. In conclusion, the results demonstrated that DBDCT caused the neurotoxicity by inducing apoptosis via mitochondria-mediated pathway.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Compuestos Orgánicos de Estaño
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Encéfalo
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Mitocondrias
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Antineoplásicos
Límite:
Animals
Idioma:
En
Revista:
Toxicol In Vitro
Asunto de la revista:
TOXICOLOGIA
Año:
2013
Tipo del documento:
Article