Enhancement of Activity of la,25-Dihydroxyvitamin D3 for Growth Inhibition and Differentiation Induction of Human Myelomonocytic Leukemia Cells by Tretinoin Tocoferil, an a-Tocopherol Ester of All-trans Retinoic Acid
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چکیده
Tretinoin tocoferil is an a-tocopherol ester of all-trans retinoic acid (RA) and safely used in the treatment of skin ulcer. Tretinoin tocoferil inhibited proliferation of human promyelocytic leukemia HL-60 cells and induced granulocytic differentiation of the cells, but less than RA. a-Tocopherol did not affect differentiation of HL-60 cells, but at high concentrations enhanced its nitroblue tetrazolium (NBT)-reducing activity and expression of surface antigen CD11 b, which are markers of myelomonocytic differentiation induced by RA. Tretinoin tocoferil increased NBT reduction in HL-60 cells treated with RA. It also enhanced the differentiation of HL60 cells induced by dimethyl sulfoxide, phorbol-12-myristate 13-acetate or Ia,Zfi-dihydroxyvitamin D3 (VD3 1. In combina-
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Acute promyelocytic leukemia (APL) has a specific genetic rearrangement between the retinoic acid receptor (RAR)-alpha gene and the pml nuclear protein gene. All-trans retinoic acid (ATRA) induces granulocytic differentiation of APL-derived cells and is used to treat APL patients. However, ATRA interacts with normal cells with RAR throughout the entire body, and when used at high doses or over ...
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