ISSN:
0730-2312
Keywords:
vitamin D3
;
differentiation
;
intracellular calcium
;
store-dependent calcium influx
;
cell cycle blocks
;
Life and Medical Sciences
;
Cell & Developmental Biology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
Notes:
Numerous vitamin D3 analogs (VDAs) can inhibit the proliferation of cells from several types of human malignancies. The physiologically active form of vitamin D3, 1,25-dihydroxyvitamin D3(1,25D3), is formed by successive hydroxylations of cholecalciferol at the 25 and 1α positions. In this study we examined the effects of the absence of the 1α(OH) group, introduction of a double bond in position 16, and further modifications at the 23, 26, and 27 positions in the side chain on the potency of the VDAs. The parameters studied were the rapidity of the induction of monocytic differentiation, the cell cycle traverse, and the effects of VDAs on intracellular calcium homeostasis in HL60 cells. The results show that (1) 1,25D3 derivatives which lack the 1α(OH) group have little differentiation-inducing activity, (2) hexafluorination (6F) of the terminal methyl groups in the side chain partially restores the activity of 1α-desoxy compounds and potentiates the activity of 1α hydroxylated compounds, and (3) 25-(OH)-16,23E-diene-26,27-hexafluoro-vitamin D3 (Ro25-9887) alone among the twelve compounds tested induces differentiation with only minimal changes in the basal levels of intracellular calcium and store-dependent calcium influx in HL60 cells. Addition of 1α(OH) group to this compound increases its differentiation-inducing activity but also elevates basal calcium level. The results suggest that altered calcium homeostasis is not an obligatory component of HL60 leukemia cell differentiation, and that Ro25-9887 and related VDAs may be suitable for testing as components of anti-leukemic therapy. © 1996 Wiley-Liss, Inc.
Additional Material:
10 Ill.
Type of Medium:
Electronic Resource
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