(-)-Epigallocatechin-3-gallate inhibits nasopharyngeal cancer stem cell self-renewal and migration and reverses the epithelial-mesenchymal transition via NF-κB p65 inactivation.
Tumour Biol
; 36(4): 2747-61, 2015 Apr.
Article
em En
| MEDLINE
| ID: mdl-25487615
The cancer stem cell (CSC) theory states that many types of cancer, including nasopharyngeal cancer (NPC), are initiated from and maintained by CSCs, which may be responsible for tumor relapse and resistance to therapy. It is imperative that nasopharyngeal cancer stem cells (NPCSCs) be specifically targeted to eradicate NPC and prevent recurrence. Epigallocatechin-3-gallate (EGCG) inhibits cancer progression by attenuating NF-κB p65 activity, which is upregulated in CSCs and plays an important role in epithelial-mesenchymal transition (EMT). The purpose of this study is to confirm the self-renewal and migration inhibitory effects of EGCG toward NPCSCs and to clarify its mechanism of activity. We enriched and characterized NPCSCs by collecting spheroid-derived cells grown in serum-free medium (SFM) and examined the effects of EGCG on the characteristics of NPCSCs and studied the underlying mechanisms using soft agar colony assays, transwell migration assays, reverse transcriptase polymerase chain reaction (RT-PCR), Western blot analysis, immunofluorescence staining, and xenograft studies. NPC spheroids enriched from NPC cell lines acquired CSC traits and underwent EMT. EGCG inhibited the NPCSCs' self-renewal and migration and reversed EMT, and combined treatment with EGCG and cisplatin reduced the growth of CSC tumor xenografts. Moreover, EGCG inhibited NF-κB p65 activity by modulating the cellular localization of p65 and decreasing the transcriptional regulation of NF-κB p65 on Twist1 expression. NF-κB p65 is a novel therapeutic target in NPCSCs, and the inhibition of activated NF-κB p65 in CSCs by EGCG may offer an effective treatment for NPC.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Neoplásicas
/
Proteínas de Transporte
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Catequina
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Neoplasias Nasofaríngeas
/
Proteínas de Neoplasias
Limite:
Humans
Idioma:
En
Revista:
Tumour Biol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2015
Tipo de documento:
Article