Water-soluble, dextran-linked retinal: preparation, vitamin A-like activity in rats, and effects on melanoma cells.
A new, water-soluble, polymer-linked form of retinal was synthesized and tested for its ability to support the growth of vitamin A-deficient noninbred Holtzman rats and to inhibit the proliferation of melanoma cells in culture. Retinal was conjugated to the hydrazide of carboxymethyldextran in the presence of alpha-and beta-cyclodextrins. The aqueous solutions of the product contained between 200 and 1,000 micrograms retinal/ml as opposed to the low water solubility (< 0.01 micrograms/ml) of retinal itself. The retinal-dextran complex, although barely resorbed from the gastrointestinal tract, supported the growth of rats fed a vitamin A-deficient diet when administered ip at 2.3 mumol of retinal equivalent/kg body weight. Retinal and the retinal-dextran complex exhibited differential cytotoxicity toward S91 melanoma cells and caused cell lysis at 10 and 500 microM (retinal residue), respectively. At noncytotoxic doses both free retinal and its dextran-linked derivative reduced the cell proliferation rate in a time- and dose-dependent fashion with median inhibitory doses of 1 and 4 microM (retinal residue), respectively. These data demonstrated that the water-soluble retinal-dextran complex retained certain biologic activities of retinal and was less cytotoxic.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D003911:Dextrans / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D008297:Male; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D051381:Rats; D012172:Retinaldehyde / Q000494:pharmacology* / Q000627:therapeutic use; D014801:Vitamin A / Q000031:analogs & derivatives*; D014802:Vitamin A Deficiency / Q000188:drug therapy
D003911:Dextrans; D014801:Vitamin A; D012172:Retinaldehyde