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 promyelocytic leukemia cells. In this study we demonstrate that clofibric acid, a well known peroxisome proliferator in rodent, augments the differentiation caused by 0.01 microM and 0.1 microM all-trans retinoic acid, and by 0.3 and 3 microM all-trans retinol. Clofibric acid alone has only marginal effects on the myeloid differentiation, whereas clofibric acid together with the glucocorticoid analogue dexamethasone gives a larger effect. Exposure of cultures to retinoid inhibits the growth of the cells, but despite the increased differentiation addition of clofibric acid to the medium does not further inhibit the growth. HL-60 cells express the nuclear receptor NUCI, a human receptor related to the peroxisome proliferator activated receptor (PPAR).
Nilsson
A
A
Institute for Nutrition Research, School of Medicine, University of Oslo, Norway.
Farrants
A K
AK
Nesland
J M
JM
Finstad
H S
HS
Pedersen
J I
JI
D002454:Cell Differentiation / Q000187:drug effects*; D002995:Clofibric Acid / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D004357:Drug Synergism; D018922:HL-60 Cells; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D012176:Retinoids / Q000494:pharmacology*
D000960:Hypolipidemic Agents; D018160:Receptors, Cytoplasmic and Nuclear; D012176:Retinoids; D002995:Clofibric Acid; D003907:Dexamethasone