Romidepsin (FK228/depsipeptide) controls growth and induces apoptosis in neuroblastoma tumor cells

Jyoti Panicker, Zhijie Li, Christine McMahon, Caroline Sizer, Kenneth Steadman, Richard Piekarz, Susan E. Bates, Carol J. Thiele

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

As histone deacetylase inhibitors such as romidepsin (depsipeptide, FK228) complete successful Phase I clinical trials in pediatric solid tumors, it is important that their mechanisms of action are delineated in order to inform the development of subsequent clinical trials as single agents or in combination therapies. In this study, we evaluate the effect of romidepsin as a single agent on a number of different neuroblastoma (NB) cell lines. We find that the growth of 6/6 human NB tumor cell lines but not an immortalized fibroblast cell line (NIH3T3) is inhibited by romidepsin (IC50 = 1-6.5 ng/ml) after 72 h of treatment. Romidepsin shows selective dose-dependent cytotoxicity in both single copy and N-myc amplified NB cell lines, in cell lines with wild type or mutant p53 and those containing Alk mutations. the decrease in cell proliferation is accompanied by caspase-dependent apoptosis as shown by PARP cleavage, an accumulation of cells in the sub-G1 phase of the cell cycle and the ability of a pan-caspase inhibitor to reduce cell death. Romidepsin inhibits the growth of subcutaneous NB xenografts in a dose dependent manner in immunocompromised mice. Furthermore, romidepsin induces expression of genes such as p21 and expression of p75 and NTRK (TrkA) which are more highly expressed in the tumors from NB patients that have a good prognosis. These studies support continued investigations into the therapeutic activity of romidepsin in NB.

Original languageEnglish (US)
Pages (from-to)1830-1838
Number of pages9
JournalCell Cycle
Volume9
Issue number9
DOIs
StatePublished - May 1 2010

Keywords

  • Apoptosis
  • Depsipeptide
  • FK228
  • HDAC inhibitor
  • Neuroblastoma
  • Romidepsin

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Romidepsin (FK228/depsipeptide) controls growth and induces apoptosis in neuroblastoma tumor cells'. Together they form a unique fingerprint.

  • Cite this

    Panicker, J., Li, Z., McMahon, C., Sizer, C., Steadman, K., Piekarz, R., Bates, S. E., & Thiele, C. J. (2010). Romidepsin (FK228/depsipeptide) controls growth and induces apoptosis in neuroblastoma tumor cells. Cell Cycle, 9(9), 1830-1838. https://doi.org/10.4161/cc.9.9.11543