Honokiol Enhances TRAIL-Mediated Apoptosis through STAMBPL1-Induced Survivin and c-FLIP Degradation.
Biomolecules
; 9(12)2019 12 06.
Article
em En
| MEDLINE
| ID: mdl-31817770
Honokiol is a natural biphenolic compound extracted from traditional Chinese medicine Magnolia species, which have been known to display various biological effects including anti-cancer, anti-proliferative, anti-angiogenic, and anti-metastatic activities in cancer cells. Here, we found that honokiol sensitizes cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through downregulation of anti-apoptotic proteins survivin and c-FLIP. Ectopic expression of survivin and c-FLIP markedly abolished honokiol and TRAIL-induced apoptosis. Mechanistically, honokiol induced protein degradation of c-FLIP and survivin through STAMBPL1, a deubiquitinase. STAMBPL1 interacted with survivin and c-FLIP, resulted in reduction of ubiquitination. Knockdown of STAMBPL1 reduced survivin and c-FLIP protein levels, while overexpression of STAMBPL1 inhibited honokinol-induced survivin and c-FLIP degradation. Our findings provided that honokiol could overcome TRAIL resistance through survivin and c-FLIP degradation induced by inhibition of STAMBPL1 expression.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Medicinas Tradicionais:
Medicinas_tradicionales_de_asia
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Medicina_china
Assunto principal:
Peptídeo Hidrolases
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Compostos de Bifenilo
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Lignanas
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Ligante Indutor de Apoptose Relacionado a TNF
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Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD
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Survivina
Idioma:
En
Revista:
Biomolecules
Ano de publicação:
2019
Tipo de documento:
Article