Effects of histone deacetylase inhibitors, sodium phenyl butyrate and vitamin B3, in combination with retinoic acid on granulocytic differentiation of human promyelocytic leukemia HL-60 cells.
Water-soluble vitamin B3, niacin, and its related compounds were suggested to be applicable for medical use. In this article, we examined the anti-leukemic effects of two distinct histone deacetylase (HDAC1 and Sir2) inhibitors, sodium phenyl butyrate (PB) and vitamin B3, respectively, on human promyelocytic leukemia cells HL-60, using HDACIs alone and in combination with all trans retinoic acid (RA). We demonstrated that the HDACI combinations exert different effects on cell cycle arrest and differentiation as determined by nitro blue reduction and the expression of the early myeloid differentiation marker CD11b. The most beneficial effects were found by use of 6-h pretreatment with PB and vitamin B3 before the exposition to RA alone or in combination with vitamin B3, showing significant acceleration and a high level of granulocytic differentiation. The effects were associated with a rapid histone H4 acetylation and later histone H3 modifications. Our results suggest that the use of two HDACI altogether before the induction of differentiation and acting via chromatin remodeling may be promising for the treatment of acute promyelocytic leukemia.
Merzvinskyte
Rasa
R
Department of Developmental Biology, Institute of Biochemistry, LT-08662 Vilnius, Lithuania.
Treigyte
Grazina
G
Savickiene
Jurate
J
Magnusson
Karl-Eric
KE
Navakauskiene
Ruta
R
D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D004338:Drug Combinations; D006098:Granulocytes / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D018922:HL-60 Cells; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000502:physiology; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D009536:Niacinamide / Q000502:physiology*; D010654:Phenylbutyrates / Q000494:pharmacology*; D014212:Tretinoin / Q000502:physiology*
D004338:Drug Combinations; D056572:Histone Deacetylase Inhibitors; D010654:Phenylbutyrates; D009536:Niacinamide; D014212:Tretinoin; D006655:Histone Deacetylases