Effects of Retinoid -Glucuronides and N-Retinoyl Amines on the Differentiation of HL-60 Cells in Vitro

Retinoyl β-glucuronide and retinyl β-glucuronide, which are naturally occurring water-soluble metabolites of vitamin A, induce the granulocytic differentiation of HL-60 cells in vitro, as evidenced by an increased reduction of nitroblue tetrazolium. The relative effectiveness of various retinoids in differentiation is retinoic acid > retinoyl β-glucuronide > retinyl β-glucuronide. Under the selected assay conditions, retinol, hydroxyphenyl-retinamide, retinamide, and N-retinoyl-phenylalanine are essentially inactive in differentiation. At concentrations of retinoids from 10-9 to 10-5M, cell viability was best with the retinoid β-glucuronides and retinamide, less with retinoic acid and retinol, and poorest with the N-retinoyl aromatic amines. Cellular growth was depressed only slightly by retinyl β-glucuronide and retinamide, but to a greater degree by the other derivatives. Retinoyl β-glucuronide was hydrolyzed in part to retinoic acid, whereas retinyl β-glucuronide was cleaved to retinol, if at all, at a very slow rate. Under the selected assay conditions, retinoic acid and the retinoid β-glucuronides primarily induce the differentiation of HL-60 cells, whereas the N-retinoyl aromatic amines show cytotoxicity.