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  • Sensitization of mesothelioma to TRAIL apoptosis by inhibition of histone deacetylase: role of Bcl-xL down-regulation

    Author(s)
    Neuzil, H
    Swettenham, E
    Gellert, N
    Griffith University Author(s)
    Neuzil, Jiri
    Year published
    2004
    Metadata
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    Abstract
    The TNF-related apoptosis-inducing ligand (TRAIL) is an immunological inducer of apoptosis selectively killing many, but not all, cancer cells. Malignant mesothelioma (MM) is fatal neoplasia with no current treatment, most likely due to high resistance of MM cells towards inducers of apoptosis, including TRAIL. We studied whether inhibition of histone deacetylase (HDAC), recently shown to sensitize malignant cells to a variety of apoptogenic substances, renders MM cells susceptible to TRAIL. Indeed, sub-apoptotic doses of the HDAC inhibitor suberohydroxamic acid (SBHA) sensitized MM cells to TRAIL apoptosis. Of the apoptotic ...
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    The TNF-related apoptosis-inducing ligand (TRAIL) is an immunological inducer of apoptosis selectively killing many, but not all, cancer cells. Malignant mesothelioma (MM) is fatal neoplasia with no current treatment, most likely due to high resistance of MM cells towards inducers of apoptosis, including TRAIL. We studied whether inhibition of histone deacetylase (HDAC), recently shown to sensitize malignant cells to a variety of apoptogenic substances, renders MM cells susceptible to TRAIL. Indeed, sub-apoptotic doses of the HDAC inhibitor suberohydroxamic acid (SBHA) sensitized MM cells to TRAIL apoptosis. Of the apoptotic mediators tested, the anti-apoptotic protein Bcl-xL was strongly down-regulated by combined treatment of the cells with SBHA and TRAIL but not by the HDAC inhibitor alone, while little or no change in the expression of other Bcl-2 family members highly expressed in MM cells, including Mcl-1 and Bax, was observed. Our data suggest a cross-talk between HDAC inhibition and TRAIL that results in modulation of expression of specific apoptotic mediators, and point to the potential of their combinatorial use in treatment of TRAIL-resistant neoplastic disease.
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    Journal Title
    Biochemical and biophysical research communications
    Volume
    314
    Issue
    1
    Publisher URI
    http://www.elsevier.com/wps/find/journaldescription.cws_home/622790/description#description
    DOI
    https://doi.org/10.1016/j.bbrc.2003.12.074
    Copyright Statement
    © 2004 Elsevier : Reproduced in accordance with the copyright policy of the publisher : This journal is available online - use hypertext links.
    Subject
    Medicinal and biomolecular chemistry
    Biochemistry and cell biology
    Medical biochemistry and metabolomics
    Publication URI
    http://hdl.handle.net/10072/5675
    Collection
    • Journal articles

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