Histone deacetylase inhibitors induce cell death in supratentorial primitive neuroectodermal tumor cells.

K Saravana Kumar, Jürgen Sonnemann, James F Beck

Journal: Oncology reports 2007;16(5):1047-52

PMID: 17016591

Abstract

Histone deacetylase inhibitors (HDIs) are a promising new class of antineoplastic agents with the capacity to induce differentiation and/or apoptosis of cancer cells. The objective of this study was to evaluate the activity of HDIs against supratentorial primitive neuroectodermal tumor (sPNET) cells. We show that the HDIs, suberoylanilide hydroxamic acid, sodium butyrate, and trichostatin A, induced cell death, and activated caspase-3 and -9 in a sPNET cell line, PFSK. The poly-caspase inhibitor z-VAD-fmk partially prevented the action of HDIs, as judged by determining the mitochondrial membrane potential and by quantifying internucleosomal DNA fragmentation. In conclusion, the HDIs explored possess potent activity against sPNET cells, suggesting that HDIs may be effective in the treatment of sPNET.

Address: Research Center of Pharmacology and Experimental Therapeutics, Ernst Moritz Arndt University of Greifswald, D-17487 Greifswald, Germany.

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MeSH Terms: Acetylation, Apoptosis, Butyrates, Caspase 3, Caspase 9, DNA Fragmentation, Enzyme Activation, Histone Deacetylase Inhibitors, Histone Deacetylases, Histones, Humans, Hydroxamic Acids, Membrane Potential, Mitochondrial, Neuroectodermal Tumors, Primitive, Protein Serine-Threonine Kinases, Supratentorial Neoplasms, Vorinostat, p21-Activated Kinases