title: 3,5,3'-Triiodothyronine stimulates retinoic acid-induced differentiation in HL-60 cells.
abstract: The human acute promyelocytic leukemia (APL) cell line HL-60 differentiates to functionally mature granulocytes by incubation with all-trans-retinoic acid (RA). Since T3 and RA are important in cell differentiation and development, and since their receptors are highly homological, we investigated the T3 effects on RA-induced HL-60 cell differentiation. Although T3 alone did not induce cell differentiation, RA-mediated differentiation was significantly enhanced in the presence of 10(-7) M T3. This effect of T3 was considered to be mediated, at least in part, by increased intracellular cAMP, since the phosphodiesterase inhibitor enhanced, and the protein kinase A antagonist partially blocked, T3 potentiation. When HL-60 cells were pretreated with RA for 20 h, T3 alone stimulated the cell differentiation. The time-course study showed that incubation with RA for 12 h was necessary for HL-60 cells to be primed to respond to T3 for differentiation. The present finding that T3 potentiates RA-induced HL-60 cell differentiation may raise the possibility that T3 supplement increases clinical remission in APL patients who are treated with RA.
authors.affiliation: Department of Internal Medicine, Kyoto University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Miyoshi
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: T
authors.initials: T
authors.lastname: Tagami
authors.forename: S
authors.initials: S
authors.lastname: Sasaki
authors.forename: K
authors.initials: K
authors.lastname: Nakao
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D001665:Binding Sites; D002454:Cell Differentiation / Q000187:drug effects*; D002467:Cell Nucleus / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology; D004357:Drug Synergism; D006098:Granulocytes; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D014212:Tretinoin / Q000494:pharmacology*; D014284:Triiodothyronine / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D014284:Triiodothyronine; D014212:Tretinoin; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine