Silibinin might be useful in treating ALK-positive anaplastic large cell lymphoma. - GreenMedInfo Summary
Silibinin suppresses NPM-ALK, potently induces apoptosis and enhances chemosensitivity in ALK-positive anaplastic large cell lymphoma.
Leuk Lymphoma. 2015 Jul 1:1-27. Epub 2015 Jul 1. PMID: 26133723
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, we report 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, we 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 subset expressing the transcriptional activity of Sox2, an embryonic stem cell marker. To conclude, our findings suggest that silibinin might be useful in treating ALK(+)ALCL.