Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tretinoin tocoferil is an alpha-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. alpha-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 CD11b, 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 HL-60 cells induced by dimethyl sulfoxide, phorbol-12-myristate 13-acetate or 1alpha,25-dihydroxyvitamin D3 (VD3). In combination with a low concentration of VD3, it induced the NBT-reducing activity of human monoblastic U937 cells very effectively. Moreover, it enhanced the differentiation of human myelomonocytic ML-1, THP-1, P39/TSU, and P31/FUJ cells induced by VD3. In combination with VD3, it synergistically inhibited the proliferation of HL-60, U937, ML-1, THP-1, P39/TSU, and P31/FUJ cells and decreased the effective concentration of VD3 to a 10(-10) mol/L level. Because tretinoin tocoferil was reported to induce neither retinoid-related toxicity nor teratogenicity, the therapeutic advantage of the use of it in treatment of myelomonocytic leukemia is suggested.
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PMID:Enhancement of activity of 1alpha, 25-dihydroxyvitamin D3 for growth inhibition and differentiation induction of human myelomonocytic leukemia cells by tretinoin tocoferil, an alpha-tocopherol ester of all-trans retinoic acid. 860 56

Tretinoin tocoferil is an alpha-tocopherol ester of all-trans retinoic acid (ATRA) and safely used to treat skin ulcers. Tretinoin tocoferil stimulates the formation of granulation tissue in the ulcer, and enhances the migration of guinea pig macrophages and stimulates the proliferation of human skin fibroblasts. These effects are different from those of either ATRA or alpha-tocopherol. Tretinoin tocoferil induces the granulocytic differentiation of human promyelocytic leukemia HL-60 cells, and more than additively enhances cellular differentiation induced by sub-optimal concentrations of ATRA. Tretinoin tocoferil and ATRA synergistically inhibit the proliferation of HL-60 cells, suggesting that tretinoin tocoferil acts differently than ATRA on leukemia cells. Tretinoin tocoferil also enhances the differentiation of HL-60 cells induced by dimethyl sulfoxide, phorbol ester and 1alpha,25-dihydroxyvitamin D3(VD3). Tretinoin tocoferil and VD3 synergistically inhibit the proliferation and induce the differentiation of other myelomonocytic leukemia cells. Toxicity tests in animal models have shown that tretinoin tocoferil is at least 150 times less toxic than ATRA and does not induce teratogenesis. Therefore, the combination of tretinoin tocoferil and VD3 may be useful for treating myelomonocytic leukemia.
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PMID:Tretinoin tocoferil as a possible differentiation-inducing agent against myelomonocytic leukemia. 925 Jul 86