Histone deacetylase inhibitors induce cell death in supratentorial primitive neuroectodermal tumor cells.
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.
Kumar
K Saravana
KS
Research Center of Pharmacology and Experimental Therapeutics, Ernst Moritz Arndt University of Greifswald, D-17487 Greifswald, Germany.
Sonnemann
Jürgen
J
Beck
James F
JF
D000107:Acetylation / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects*; D002087:Butyrates / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018242:Neuroectodermal Tumors, Primitive / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015173:Supratentorial Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D000077337:Vorinostat; D054462:p21-Activated Kinases
D002087:Butyrates; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; C012589:trichostatin A; D000077337:Vorinostat; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D053148:Caspase 3; D053453:Caspase 9; D006655:Histone Deacetylases