Induction of HL-60 cell differentiation by water-soluble and nitrogen-containing conjugates of retinoic acid and retinol.
Retinoids induce the promyelocytic cell line, HL-60, to differentiate along the granulocytic pathway in vitro. A number of water-soluble and nitrogen-containing retinoids were synthesized in our laboratory [retinoyl-glucose (RAGL), retinyl-glucose (ROGL), retinoyl-adenosine (RADS), retinoyl-adenine (RAD), retinoyl-beta-glucuronide (beta RAG), and retinoyl-alpha-glucuronide (alpha RAG)]. These retinoids (10(-5) to 10(-8) M), as well as retinoic acid (RA) and retinol (ROL), were tested for their ability to induce the differentiation of HL-60 cells in vitro and to affect cell growth and viability during a 24- to 72-h incubation period. Differentiation was assessed by measuring the percentage of cells expressing the Mac-1 antigen on their cell surfaces. RA and the conjugates of RA were all quite active in inducing HL-60 cell differentiation, whereas ROL and ROGL had much less activity at equimolar concentrations. beta RAG, alpha RAG, RADS, and RAD were less toxic, whereas the glucose conjugates of retinol and retinoic acid (ROGL and RAGL) were both considerably more toxic than either RA or ROL at equimolar concentrations. All retinoids affected cell growth in a dose-dependent fashion. At 24 h, free RA or ROL was not detected in the cells after incubation with any of the retinoid conjugates.
Janick-Buckner
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D
Department of Biochemistry and Biophysics, Iowa State University, Ames 50011.
Barua
A B
AB
Olson
J A
JA
D002454:Cell Differentiation / Q000187:drug effects; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D012176:Retinoids / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014801:Vitamin A / Q000494:pharmacology*
D012176:Retinoids; D014801:Vitamin A; D014212:Tretinoin