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Depsipeptide induces cell death in Hodgkin lymphoma-derived cell lines by Ingo Hartlapp; Christian Pallasch; Ganna Weibert; Andrea Kemkers; Michael Hummel; Daniel Re is a Medicine article available to read on EtoBox.

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A variety of genetic and epigenetic abnormalities were characterized over the last years in Hodgkin and Reed-Sternberg (H-RS) cells of classic Hodgkin Lymphoma (cHL). It was speculated that simultaneous inhibition of multiple signalling pathways might be a promising strategy to target this tumor entity. In the present study we tested the effect of histone deacetylase (HDAC) inhibition using depsipeptide (also known as romidepsin, FK228, FR901228 or NSC-630176) in cHL cell lines in vitro. Molecular mechanisms of toxicity were analyzed using RNA expression analysis and functional assays. It is shown that depsipeptide is effective at submicromolar concentrations and acts mainly by apoptosis induction, upregulation of p21 and cell cycle inhibition in G2/M. Of special note, HDAC mediated toxicity in H-RS cells does not require RelA/p65 downregulation, which was previously shown to drive the malignant phenotype of H-RS cells. In summary, depsipeptide induced protein acetylation results in transcriptional changes of a large number of pathogenetically relevant genes and increased RelA/p65 binding activity in cHL cell lines. Our preclinical data suggest that HDAC inhibition using depsipepti

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Author

Ingo Hartlapp; Christian Pallasch; Ganna Weibert; Andrea Kemkers; Michael Hummel; Daniel Re

Publisher

Elsevier Science; Elsevier ; Elsevier Ltd.; Elsevier BV (ISSN 0145-2126)

Published

2009

Language

EN

Field

Medicine (Health Sciences)