A small-molecule triptolide suppresses angiogenesis and invasion of human anaplastic thyroid carcinoma cells via down-regulation of the nuclear factor-kappa B pathway.
Mol Pharmacol
; 75(4): 812-9, 2009 Apr.
Article
en En
| MEDLINE
| ID: mdl-19158360
ABSTRACT
Anaplastic thyroid carcinoma (ATC) is among the most aggressive malignancies known and is characterized with rapid growth, early invasion, and complete refractoriness to current therapies. Here we report that triptolide, a small molecule from a Chinese herb, could potently inhibit proliferation in vitro, angiogenesis in vivo, and invasion in a Matrigel model in human ATC cell line TA-K cells at nanomolar concentrations. We further elucidate that triptolide inhibits the nuclear factor-kappaB (NF-kappaB) transcriptional activity via blocking the association of p65 subunit with CREB-binding protein (CBP)/p300 in the early stage and via decreasing the protein level of p65 in the late stage. Expression of the NF-kappaB targeting genes cyclin D1, vascular endothelial growth factor, and urokinase-type plasminogen activator is significantly reduced by triptolide in both TA-K and 8505C human ATC cell lines, which are well known to be critical for proliferation, angiogenesis, and invasion in solid tumors. Our findings suggest that triptolide may function as a small molecule inhibitor of tumor angiogenesis and invasion and may provide novel mechanistic insights into the potential therapy for human ATC.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Fenantrenos
/
Neoplasias de la Tiroides
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Carcinoma
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Transducción de Señal
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Regulación hacia Abajo
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FN-kappa B
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Inhibidores de la Angiogénesis
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Diterpenos
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Neovascularización Patológica
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Año:
2009
Tipo del documento:
Article