title: Histone deacetylase inhibitors interact synergistically with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to induce apoptosis in carcinoma cell lines.
abstract: Both tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and histone deacetylase inhibitors (HDIs) show promise for the treatment of cancer. However, in a number of reports they have been proven ineffective to induce cell death when applied as single agents. In this study, we show that A549 lung carcinoma cells and PC-3 prostate carcinoma cells underwent substantial apoptosis when coexposed to TRAIL and either suberoylanilide hydroxamic acid, sodium butyrate or trichostatin A. HDIs and TRAIL synergized in activation of capase-3, induction of internucleosomal DNA fragmentation and promoting mitochondrial damage. Significantly, cotreatment with minimally toxic doses of HDIs and TRAIL resulted in a marked apoptotic response in both cell lines. These data provide a rationale for a more in-depth exploration into the potential of combining TRAIL and HDIs as a valuable anticancer strategy.
authors.affiliation: Peter Holtz Research Center of Pharmacology and Experimental Therapeutics, Ernst Moritz Arndt University, Greifswald, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Sonnemann
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gänge
authors.forename: K Saravana
authors.initials: KS
authors.lastname: Kumar
authors.forename: Cornelia
authors.initials: C
authors.lastname: Müller
authors.forename: Peter
authors.initials: P
authors.lastname: Bader
authors.forename: James F
authors.initials: JF
authors.lastname: Beck
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D020148:Butyric Acid / Q000627:therapeutic use; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects* / Q000201:enzymology; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008562:Membrane Glycoproteins / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*; D000077337:Vorinostat
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D020148:Butyric Acid; C012589:trichostatin A; D000077337:Vorinostat; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases
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