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.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Antineoplastic Agents / therapeutic use*
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Apoptosis / drug effects*
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Apoptosis Regulatory Proteins
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Butyric Acid / therapeutic use
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Caspase 3
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Caspases / metabolism
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Cell Line, Tumor / drug effects*
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Cell Line, Tumor / enzymology
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Drug Synergism
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Enzyme Inhibitors / therapeutic use
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Histone Deacetylase Inhibitors*
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Humans
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Hydroxamic Acids / therapeutic use
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Lung Neoplasms / drug therapy
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Male
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Membrane Glycoproteins / therapeutic use*
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Prostatic Neoplasms / drug therapy
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TNF-Related Apoptosis-Inducing Ligand
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Tumor Necrosis Factor-alpha / therapeutic use*
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Vorinostat
Substances
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Antineoplastic Agents
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Apoptosis Regulatory Proteins
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Enzyme Inhibitors
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Histone Deacetylase Inhibitors
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Hydroxamic Acids
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Membrane Glycoproteins
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TNF-Related Apoptosis-Inducing Ligand
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TNFSF10 protein, human
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Tumor Necrosis Factor-alpha
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Butyric Acid
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trichostatin A
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Vorinostat
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CASP3 protein, human
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Caspase 3
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Caspases