POTENTIATING EFFECTS OF CLOFIBRIC ACID ON THE DIFFERENTIATION OF HL-60 HUMAN PROMYELOCYTIC LEUKEMIA-CELLS INDUCED BY RETINOIDS

Retinoids induce granulocytic differentiation of HL-60 human promyeloc ytic leukemia cells. In this study we demonstrate that clofibric acid, a well known peroxisome proliferator in rodent, augments the differen tiation caused by 0.01 mu M and 0.1 mu M all-trans retinoic acid, and by 0.3 and 3 mu M all-trans retinol. Clofibric acid alone has only mar ginal effects on the myeloid differentiation, whereas clofibric acid t ogether with the glucocorticoid analogue dexamethasone gives a larger effect. Exposure of cultures to retinoid inhibits the growth of the ce lls, but despite the increased differentiation addition of clofibric a cid to the medium does not further inhibit the growth. HL-60 cells exp ress the nuclear receptor NUCI, a human receptor related to the peroxi some proliferator activated receptor (PPAR).