Silibinin suppresses NPM-ALK, potently induces apoptosis and enhances chemosensitivity in ALK-positive anaplastic large cell lymphoma.
Leuk Lymphoma
; 57(5): 1154-62, 2016 May.
Article
em En
| MEDLINE
| ID: mdl-26133723
ABSTRACT
Nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), an oncogenic fusion protein carrying constitutively active tyrosine kinase, is known to be central to the pathogenesis of ALK-positive anaplastic large cell lymphoma (ALK+ALCL). Here, it is reported that silibinin, a non-toxic naturally-occurring compound, potently suppressed NPM-ALK and effectively inhibited the growth and soft agar colony formation of ALK+ALCL cells. By western blots, it was found that silibinin efficiently suppressed the phosphorylation/activation of NPM-ALK and its key substrates/downstream mediators (including STAT3, MEK/ERK and Akt) in a time- and dose-dependent manner. Correlating with these observations, silibinin suppressed the expression of Bcl-2, survivin and JunB, all of which are found to be upregulated by NPM-ALK and pathogenetically important in ALK+ALCL. Lastly, silibinin augmented the chemosensitivity of ALK+ALCL cells to doxorubicin, particularly the small cell sub-set expressing the transcriptional activity of Sox2, an embryonic stem cell marker. To conclude, the findings suggest that silibinin might be useful in treating ALK+ALCL.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Silimarina
/
Proteínas Tirosina Quinases
/
Apoptose
/
Receptores Proteína Tirosina Quinases
/
Linfoma Anaplásico de Células Grandes
/
Resistencia a Medicamentos Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article