The mitochondrial cyclophilin D/p53 complexation mediates doxorubicin-induced non-apoptotic death of A549 lung cancer cells.
Mol Cell Biochem
; 389(1-2): 17-24, 2014 Apr.
Article
em En
| MEDLINE
| ID: mdl-24343341
ABSTRACT
Doxorubicin has displayed significant cytotoxic effects against the lung cancer cells; however, the underlying mechanisms remain inconclusive. In the current study, we provided evidence to show that mitochondrial p53 and cyclophilin D (Cyp-D) complexation is required for doxorubicin-induced death of lung cancer A549 cells. Doxorubicin induced both apoptotic and non-apoptotic death of A549 cells. Cyclosporine A (CsA), the Cyp-D inhibitor, and Cyp-D silencing were prevented doxorubicin-induced non-apoptotic death of A549 cells, while cells overexpressing Cyp-D were hyper-sensitive to doxorubicin. In A549 cells, doxorubicin-activated p53, the latter translocated to mitochondria and physically interacted with Cyp-D. The p53/Cyp-D mitochondrial complexation was prevented by CsA or Cyp-D silencing, or by p53 inhibitor pifithrin-α. Significantly, doxorubicin-induced anti-tumor ability in vivo was also compromised by CsA, or when Cyp-D was silenced. Together, these data suggested that Dox-induced non-apoptotic death of A549 cells requires mitochondrial Cyp-D-p53 complexation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doxorrubicina
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Proteína Supressora de Tumor p53
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Morte Celular
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Ciclofilinas
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Neoplasias Pulmonares
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Mitocôndrias
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article