Abstract
A low concentration of differentiation inducers such as dimethylsulphoxide (DMSO), sodium butyrate, hexamethylene bisacetamide and sodium phenylacetate greatly enhanced the antiproliferative effect in vitro and in vivo of interferon alpha (IFN-alpha) to several human lung adenocarcinoma cells. The agents induced morphological changes in the adenocarcinoma cells and the agents together with IFN-alpha-induced alkaline phosphatase activity, which is a typical marker of type II pneumocyte maturation. To understand the mechanism of the DMSO-enhanced interferon sensitivity, we examined the effect of DMSO on high-affinity IFN-alpha receptor and interferon-stimulated promoter-binding factors. The lung adenocarcinoma cells were not impaired in IFN-alpha receptor and interferon-stimulated gene transactivation factor 3 (ISGF-3). Our data suggest that the enhancement of interferon sensitivity in the lung adenocarcinoma cells acts downstream of the activation of ISGF-3.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetamides / pharmacology
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Adenocarcinoma / pathology*
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Adenocarcinoma / therapy
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Alkaline Phosphatase / biosynthesis
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Animals
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Antineoplastic Agents / therapeutic use
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Antineoplastic Agents / toxicity*
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Biomarkers
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Butyrates / pharmacology
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Butyric Acid
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Carcinoma, Large Cell
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Carcinoma, Small Cell
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Carcinoma, Squamous Cell
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Cell Differentiation*
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Cell Division / drug effects
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Cell Line
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Dimethyl Sulfoxide / pharmacology
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Dose-Response Relationship, Drug
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Drug Synergism
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Enzyme Induction
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Female
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Humans
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Interferon-alpha / therapeutic use
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Interferon-alpha / toxicity*
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Kinetics
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Lung Neoplasms / pathology*
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Lung Neoplasms / therapy
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Mice
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Mice, Nude
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Phenylacetates / pharmacology
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Promoter Regions, Genetic
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Receptor, Interferon alpha-beta
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Receptors, Interferon / metabolism
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Transplantation, Heterologous
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Tumor Cells, Cultured
Substances
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Acetamides
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Antineoplastic Agents
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Biomarkers
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Butyrates
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Interferon-alpha
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Phenylacetates
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Receptors, Interferon
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Butyric Acid
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Receptor, Interferon alpha-beta
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Alkaline Phosphatase
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phenylacetic acid
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hexamethylene bisacetamide
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Dimethyl Sulfoxide