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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
M Makishima, Y Kanatani, Y Yamamoto-Yamaguchi and Y Honma
Department of Chemotherapy, Saitoma Cancer Center Research Institute,
Ina-machi, Japan.
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.
Volume 87,
Issue 8,
pp. 3384-3394,
04/15/1996
Copyright © 1996 by The American Society of Hematology
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