Halothane Potentiates the Antitumor Activity of Gamma-interferon and Mimics Calmodulin-blocking Agents
Autor: | Igor Espinoza-Delgado, Dan L. Longo, Steven C. Hall, Henry C. Stevenson, S. J. Rudnick, G. W. Stevenson |
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Rok vydání: | 1991 |
Předmět: |
Calmodulin
biology Cell Survival business.industry Antineoplastic Agents Drug Synergism Trifluoperazine Pharmacology In vitro Interferon-gamma Cytolysis Anesthesiology and Pain Medicine Cell culture Tumor Cells Cultured biology.protein Humans Medicine Interferon gamma Halothane business Cytotoxicity medicine.drug |
Zdroj: | Anesthesiology. 74:115-119 |
ISSN: | 0003-3022 |
DOI: | 10.1097/00000542-199101000-00019 |
Popis: | This study reports effects of halothane on tumor cells in vitro. Cells from the human colon cancer cell line HT-29 were exposed to various concentrations of halothane for 8-72 h. The effect of this exposure on this colon cancer cell line, with and without coincubation with the biologic response modifier gamma-interferon (IFN-gamma), was studied. Using the tumor target cell survival (TTCS) assay, concentrations of halothane from 0.5 to 2% markedly augmented the antitumor activities of IFN-gamma against HT-29. The tumor cell cytostatic effects of IFN-gamma in the 0.75-6-unit/ml range were increased nearly 400% by concentrations of halothane as low as 1%. These results were confirmed in a separate cytolytic assay (Indium-111 release assay), which revealed that halothane concentrations in the 2-4% range markedly increased the cytolytic capacity of IFN-gamma at doses of IFN-gamma between 75 and 1,250 units/ml. The cytolytic activity of IFN-gamma was increased nearly 300% by doses of halothane as low as 1%. A nearly identical pattern of augmentation of IFN-gamma-induced antitumor activity was observed when the known calmodulin inhibitor trifluoperazine (TFP) was coincubated with IFN-gamma. At concentrations of 4-10 microM, the antitumor activity of IFN-gamma was increased nearly 400%. These observations suggest that the pattern of halothane potentiation of the antitumor activity of IFN-gamma is similar to that exhibited by known calmodulin inhibitors. |
Databáze: | OpenAIRE |
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