Enhancement of sensitivity of human lung adenocarcinoma cells to growth-inhibitory activity of interferon alpha by differentiation-inducing agents.
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.
Goto
I
I
Department of Chemotherapy, Saitama Cancer Center, Japan.
Yamamoto-Yamaguchi
Y
Y
Honma
Y
Y
D000081:Acetamides / Q000494:pharmacology; D000230:Adenocarcinoma / Q000473:pathology* / Q000628:therapy; D000469:Alkaline Phosphatase / Q000096:biosynthesis; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity*; D015415:Biomarkers; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D018287:Carcinoma, Large Cell; D018288:Carcinoma, Small Cell; D002294:Carcinoma, Squamous Cell; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use / Q000633:toxicity*; D007700:Kinetics; D008175:Lung Neoplasms / Q000473:pathology* / Q000628:therapy; D051379:Mice; D008819:Mice, Nude; D010648:Phenylacetates / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000378:metabolism; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000081:Acetamides; D000970:Antineoplastic Agents; D015415:Biomarkers; D002087:Butyrates; D016898:Interferon-alpha; D010648:Phenylacetates; D017471:Receptors, Interferon; D020148:Butyric Acid; D053633:Receptor, Interferon alpha-beta; D000469:Alkaline Phosphatase; C025136:phenylacetic acid; C014026:hexamethylene bisacetamide; D004121:Dimethyl Sulfoxide