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Histone deacetylase inhibitors sensitize human colonic adenocarcinoma cell lines to TNF-related apoptosis inducing ligand-mediated apoptosis

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Histone deacetylase inhibitor (HDAI) induces accumulation of highly acetylated histones by inhibiting the activity of histone deacetylase and inhibits cell proliferation, induces differentiation, and promotes apoptosis. TNF-related apoptosis inducing ligand (TRAIL) induces apoptosis in various human cancer cells, a promising observation because it raises the possibility of a death ligand selectively for tumor cells. However, resistance to TRAIL-induced apoptosis was seen in colonic adenocarcinoma cell lines. So we investigated whether human colonic adenocarcinoma cell lines can be sensitized to TRAIL-induced apoptosis by the addition of HDAI. We investigated sensitivity to histone deacetylase inhibitor in colonic adenocarcinoma cell lines using the MTT assay. Cell viability decreased with sodium butyrate (SB) and trichostatinA (TSA) in a dose-dependent manner in LS 180 and HT-29 cells. Nuclear condensation and fragmentation were observed by DAPI staining after 24 h stimulation with SB or TSA in LS 180 cells. We also investigated the combination of HDAI and TNF family members (TRAIL, anti-Fas antibody or TNFα) in colonic adenocarcinoma cell lines. HDAI augmented TNF family-related apoptosis in LS 180 cells and HT-29 cells. HDAI sensitizes human colonic adenocarcinoma cell lines to TRAIL-mediated apoptosis. HDAI may be useful as an adjuvant agent for TRAIL in the treatment of human colonic adenocarcinomas that are resistant to TRAIL.
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Document Type: Research Article

Affiliations: First Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie 514-8507, Japan

Publication date: January 1, 2002

More about this publication?
  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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