Downregulation of cFLIP and upregulation of DR5 by cantharidin sensitizes TRAILmediated apoptosis in prostate cancer cells via autophagy flux.
Int J Mol Med
; 46(1): 280-288, 2020 Jul.
Article
em En
| MEDLINE
| ID: mdl-32319535
ABSTRACT
Tumor necrosis factor (TNF)related apoptosisinducing ligand (TRAIL), a type II transmembrane protein, is a part of the TNF superfamily of cytokines. Cantharidin, a type of terpenoid, is extracted from the blister beetles (Mylabris genus) used in Traditional Chinese Medicine. Cantharidin elicits antibiotic, antiviral and antitumor effects, and can affect the immune response. The present study demonstrated that a cantharidin and TRAIL combination treatment regimen elicited a synergistic outcome in TRAILresistant DU145 cells. Notably, it was also identified that cantharidin treatment initiated the downregulation of cellular FLICElike inhibitory protein (cFLIP) and upregulation of death receptor 5 (DR5), and sensitized cells to TRAILmediated apoptosis by initiating autophagy flux. In addition, cantharidin treatment increased lipidmodified microtubuleassociated proteins 1A/1B light chain 3B expression and significantly attenuated sequestosome 1 expression. Attenuation of autophagy flux by a specific inhibitor such as chloroquine and genetic modification using ATG5 small interfering RNA abrogated the cantharidinmediated TRAILinduced apoptosis. Overall, the results of the present study revealed that cantharidin effectively sensitized cells to TRAILmediated apoptosis and its effects are likely to be mediated by autophagy, the downregulation of cFLIP and the upregulation of DR5. They also suggested that the combination of cantharidin and TRAIL may be a successful therapeutic strategy for TRAILresistant prostate cancer.
Texto completo:
1
Base de dados:
MEDLINE
Medicinas Tradicionais:
Medicinas_tradicionales_de_asia
/
Medicina_china
Assunto principal:
Cantaridina
/
Ligante Indutor de Apoptose Relacionado a TNF
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Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD
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Receptores do Ligante Indutor de Apoptose Relacionado a TNF
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Int J Mol Med
Ano de publicação:
2020
Tipo de documento:
Article