Reduction of TRAIL-induced Mcl-1 and cIAP2 by c-Myc or sorafenib sensitizes resistant human cancer cells to TRAIL-induced death.
Cancer Cell
; 12(1): 66-80, 2007 Jul.
Article
em En
| MEDLINE
| ID: mdl-17613437
ABSTRACT
Cells expressing oncogenic c-Myc are sensitized to TNF superfamily proteins. c-Myc also is an important factor in determining whether a cell is sensitive to TRAIL-induced apoptosis, and it is well established that the mitochondrial pathway is essential for apoptosis induced by c-Myc. We investigated whether c-Myc action on the mitochondria is required for TRAIL sensitivity and found that Myc sensitized cells with defective intrinsic signaling to TRAIL. TRAIL induced expression of antiapoptotic Mcl-1 and cIAP2 through activation of NF-kappaB. Both Myc and the multikinase inhibitor sorafenib block NF-kappaB. Combining sorafenib with TRAIL in vivo showed dramatic efficacy in TRAIL-resistant tumor xenografts. We propose the combination of TRAIL with sorafenib holds promise for further development.
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Base de dados:
MEDLINE
Assunto principal:
Piridinas
/
Benzenossulfonatos
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Proteínas Proto-Oncogênicas c-myc
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Apoptose
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Proteínas Proto-Oncogênicas c-bcl-2
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Proteínas Inibidoras de Apoptose
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Ligante Indutor de Apoptose Relacionado a TNF
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Proteínas de Neoplasias
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Antineoplásicos
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article