Halothane potentiates the antitumor activity of gamma-interferon and mimics calmodulin-blocking agents.
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.
Rudnick
S
S
Northwestern University Medical School, Chicago, Illinois.
Stevenson
G W
GW
Hall
S C
SC
Espinoza-Delgado
I
I
Stevenson
H C
HC
Longo
D L
DL
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D006221:Halothane / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D014268:Trifluoperazine / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D002147:Calmodulin; D014268:Trifluoperazine; D007371:Interferon-gamma; D006221:Halothane