Potentiation of retinoid-induced differentiation of HL-60 and U937 cell lines by cytokines.
Retinoids varied in their capacity to induce differentiation in HL-60 cells in this order: Ro 13-6307, tretinoin, isotretinoin, acitretin and Ro 13-7410 (high to low). In contrast, retinoids lacking a polar carboxylic acid, such as temarotene and Ro 14-6113, were inactive. Various cytokines had no differentiation-inducing effect by themselves. However, the addition of cytokines to retinoids increased differentiation. Combined with tretinoin, cytokines increased differentiation in this order: interferon (IFN) gamma, granulocyte colony-stimulating factor, interleukin-1 alpha (IL-1 alpha), IL-4, tumour necrosis factor alpha and IFN-alpha. Combination of cytokines with isotretinoin, acitretin, Ro 13-7410, and Ro 13-6307 showed a similar pattern of potentiation to that of tretinoin. Temarotene or Ro 14-6113 did not induce differentiation, alone or with cytokines. Combinations of cytokines were not synergistic in the presence of retinoids; antagonism was even observed. In U937 cells, lower levels of differentiation-induction were observed. Potentiation of the differentiation-inducing effect of retinoids by cytokines might indicate a clinical differentiation therapy of tumours.
Peck
R
R
Pharmaceutical Research, F. Hoffmann-La Roche Ltd, Basle, Switzerland.
Bollag
W
W
D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology*; D012176:Retinoids / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D016207:Cytokines; D012176:Retinoids