Butyric monosaccharide ester-induced cell differentiation and anti-tumor activity in mice. Importance of their prolonged biological effect for clinical applications in cancer therapy.
The interest of butyric salts is based on their capacity to promote differentiation of malignant cells and inhibition of tumor development. The phenotypic modifications are rapidly reversible and require the continuous presence of butyric salts in the target area, which raises problems for therapeutic applications. We show here that the covalent binding of n-butyric acid on natural polyhydroxylated compounds such as monosaccharides, especially 3- or 6-O-butanoyl-1,2-O-isopropylidene-alpha-D-glucofuranose, retains the majority of the biological properties of n-butyric acid. The delayed degradation of these covalent compounds is associated with an improved maintenance of cell differentiation and anti-tumor protection in mice. These butyric complexes thus seem potentially useful for therapeutic applications.
Pouillart
P
P
Laboratoire de Recherche contre les Virus, Institut National de la Santé et de la Recherche Médicale, Unité 43, Hôpital Saint Vincent-de-Paul, France.
Cerutti
I
I
Ronco
G
G
Villa
P
P
Chany
C
C
D000818:Animals; D000970:Antineoplastic Agents; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002087:Butyrates / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000517:prevention & control; D011355:Prodrugs; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D002087:Butyrates; D011355:Prodrugs; C069135:esterbut-3; C069134:esterbut-6; D001120:Arginine; C033018:arginine butyrate; D005947:Glucose