ASK1/JNK-mediated TAp63 activation controls the cell survival signal of baicalein-treated EBV-transformed B cells.
Mol Cell Biochem
; 412(1-2): 247-58, 2016 Jan.
Article
em En
| MEDLINE
| ID: mdl-26694167
Transcriptionally active p63 (TAp63) promotes cell cycle arrest, senescence, and apoptosis in several cancer cells. Migration inhibitory factor (MIF)/CD74 regulates B-cell survival through nuclear factor (NF)-κB-dependent TAp63 expression. In this study, we investigated how the level of TAp63 expression influences the induction of apoptosis in baicalein-treated EBV-transformed B cells. Baicalein induced the expression of TAp63 and apoptosis signal-regulating kinase 1 (ASK1), as well as cytotoxicity, by disrupting the mitochondrial membrane and inhibiting the activation of phosphoinositide 3-kinase (PI3K)/Akt and NF-κB. Genetic knockdown of TAp63 or ASK1 by small interfering RNA resulted in protection from apoptosis accompanied by the recovery of CD74, CD44, α4 integrin, Bcl-2, and NF-κB activation. Baicalein-induced reactive oxygen species activated the ASK1/JNK pathway with subsequent expression of TAp63. Pre-engagement with MIF/CD74 maintained the expression of CD74, CD44, and α4 integrin, as well as Syk/Src-mediated PI3K/Akt activation, in baicalein-treated EBV-transformed B cells. Meanwhile, ASK1/JNK-dependent TAp63 expression was efficiently suppressed after pre-treatment with MIF. Our results suggest that baicalein-mediated ASK1/JNK activation regulates the mitochondria-dependent apoptosis pathway through the up-regulation of TAp63 and down-regulation of NF-κB and CD74/CD44 in B-cell malignancies.
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Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Linfócitos B
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Herpesvirus Humano 4
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Proteínas Supressoras de Tumor
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Flavanonas
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MAP Quinase Quinase Quinase 5
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MAP Quinase Quinase 4
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article