Enhancement by stable butyrate derivatives of antitumor and antiviral actions of interferon.
The use of n-butyric acid has been associated with induction of cell differentiation and bypassing of genetic defects in the suppression of malignancy. This biological response modifier satisfies the requirements for specificity and low toxicity, and its use can be considered as an alternative approach to conventional cancer chemotherapy. However, a lack of clinical efficacy has been observed with butyrate and attributed mainly to the rapid metabolism of the compound. Butyric acid pro-drugs derived from monosaccharides such as 3-O-butanoyl-1,2-O-isopropylidene-alpha-D-glucofuranose (MAG = 3but) have consequently been devised. Pharmacokinetic and biological advantages of MAG = 3but have been previously described. In the present report, we have studied the effect of MAG = 3but on murine interferon-alpha, beta (IFN) anticellular, antitumor and antiviral activities. In vitro, it appears that MAG = 3but predisposes malignant MSV cells to a later, complete establishment of the antiproliferative and the cell-differentiating effects of IFN, and the antiviral action of the latter in the same line of cells infected with encephalomyocarditis (EMC) virus. In vivo, combined treatment with MAG = 3but and IFN protects mice effectively against the fatal development of ascitic sarcoma 180 TG and the lethal effect of EMC virus infection.
Pouillart
P
P
Laboratoire de Recherche contre les virus, INSERM Unité 43, Hôpital Saint Vincent de Paul, Paris, France.
Cerutti
I
I
Ronco
G
G
Villa
P
P
Chany
C
C
D000818:Animals; D002087:Butyrates / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D002461:Cell Line, Transformed / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004686:Encephalomyocarditis virus; D004769:Enterovirus Infections / Q000517:prevention & control*; D005947:Glucose / Q000031:analogs & derivatives* / Q000494:pharmacology; D016898:Interferon-alpha / Q000494:pharmacology* / Q000627:therapeutic use; D016899:Interferon-beta / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D011355:Prodrugs / Q000494:pharmacology*; D012510:Sarcoma 180 / Q000517:prevention & control*
D002087:Butyrates; D016898:Interferon-alpha; D011355:Prodrugs; C069135:esterbut-3; D016899:Interferon-beta; D005947:Glucose