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Histone deacetylase inhibitors interact synergistically with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to induce apoptosis in carcinoma cell lines

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Summary

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.

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Authors and Affiliations

  1. Peter Holtz Research Center of Pharmacology and Experimental Therapeutics, Ernst Moritz Arndt University, Greifswald, Germany

    Jürgen Sonnemann, Jennifer Gänge & K. Saravana Kumar

  2. Department of Pediatric Hematology/Oncology, Ernst Moritz Arndt University, Greifswald, Germany

    Cornelia Müller & James F. Beck

  3. Department of Pediatric Hematology/Oncology, University of Tübingen, Germany

    Peter Bader

  4. Department of Pediatric Hematology/Oncology, Ernst Moritz Arndt University, Greifswald, Germany

    James F. Beck

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  1. Jürgen Sonnemann
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  2. Jennifer Gänge
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  3. K. Saravana Kumar
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  4. Cornelia Müller
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  6. James F. Beck
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Correspondence to James F. Beck.

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Sonnemann, J., Gänge, J., Kumar, K.S. et al. Histone deacetylase inhibitors interact synergistically with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to induce apoptosis in carcinoma cell lines. Invest New Drugs 23, 99–109 (2005). https://doi.org/10.1007/s10637-005-5854-9

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  • DOI: https://doi.org/10.1007/s10637-005-5854-9

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