Attenuation of autophagy flux by 6-shogaol sensitizes human liver cancer cells to TRAIL-induced apoptosis via p53 and ROS.
Int J Mol Med
; 43(2): 701-708, 2019 Feb.
Article
em En
| MEDLINE
| ID: mdl-30483736
ABSTRACT
Tumor necrosis factor (TNF)related apoptosisinducing ligand (TRAIL) is a member of the TNF superfamily and is an antitumor drug that induces apoptosis in tumor cells with minimal or no effects on normal cells. Here, it is demonstrated that 6shogaol (6sho), a bioactive component of ginger, exerted antiinflammatory and anticancer properties, attenuated tumor cell propagation and induced TRAILmediated cell death in liver cancer cells. The current study identified a potential pathway by revealing that TRAIL and 6sho or chloroquine acted together to trigger reactive oxygen species (ROS) production, to upregulate tumorsuppressor protein 53 (p53) expression and to change the mitochondrial transmembrane potential (MTP). Treatment with NacetylLcysteine reversed these effects, restoring the MTP and attenuated ROS production and p53 expression. Interestingly, treatment with 6sho increased p62 and microtubuleassociated proteins 1A/1B light chain 3BII levels, indicating an inhibited autophagy flux. In conclusion, attenuation of 6shoinduced autophagy flux sensitized cells to TRAILinduced apoptosis via p53 and ROS, suggesting that the administration of TRAIL in combination with 6sho may be a suitable therapeutic method for the treatment of TRAILresistant Huh7 liver cells.
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Base de dados:
MEDLINE
Assunto principal:
Autofagia
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Catecóis
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Proteína Supressora de Tumor p53
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Espécies Reativas de Oxigênio
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Ligante Indutor de Apoptose Relacionado a TNF
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Neoplasias Hepáticas
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article