Inhibition of proliferation and CD25 down-regulation by retinoic acid in human adult T cell leukemia cells.
The effects of retinoic acid (RA) on the cell growth and expression of interleukin-2 (IL-2) receptors (IL-2R alpha/p55, Tac, CD25) by the human T lymphotropic virus type I (HTLV-I)-positive T cell lines, HUT102 and ATL-2 were investigated. Incubation of these cells for 48 h with either 13-cis retinoid acid (13-cis RA) or all-trans retinoic acid (ATRA) resulted in marked inhibition of cell growth, determined by 3H-thymidine incorporation, and in down-regulation of CD25 expression, determined by flow cytometry. Four HUT102 cell clones were established by limiting dilution, and 13-cis RA was shown to inhibit cell growth and CD25 expression in three of these clones (HUT102-M5, -M6 and -M7), but not in the fourth (-M8). RA did not induce growth inhibition or down-regulation of CD25 in the HTLV-I-negative T cell lines (Jurkat and MOLT-4) and in normal lymphocytes that had been stimulated with phytohemagglutinin or phorbol 12-myristate 13-acetate. We have shown that RA markedly inhibited both the cell growth and the expression of CD25 in some HTLV-I-positive T cell clones, but not in normal lymphocytes. These results suggest that RA may be suitable for the treatment of patients with adult T cell leukemia (ATL).
Miyatake
J I
JI
Third Department of Internal Medicine, Kinki University School of Medicine, Osaka, Japan.
Maeda
Y
Y
D000951:Antigens, Neoplasm / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D015368:Human T-lymphotropic virus 1; D006801:Humans; D015458:Leukemia, T-Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D010835:Phytohemagglutinins / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D013268:Stimulation, Chemical; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013936:Thymidine / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014316:Tritium; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2; D014316:Tritium; D014212:Tretinoin; D013936:Thymidine