24- and 26-homo-1,25-dihydroxyvitamin D/sub 3/: preferential activity in inducing differentiation of human leukemia cells HL-60 in vitro inducing differentiation of human leukemia cells HL-60 in vitro

Journal Article · Fri May 01 00:00:00 EDT 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.9.2610· OSTI ID:5876116

Ostrem, V K; Tanaka, Y; Prahl, J; DeLuca, H F; Ikekawa, N

1,25-Dihydroxyvitamin D/sub 3/, the hormonal form of vitamin D/sub 3/, promotes the differentiation of HL-60 human promyelocytic leukemia cells into monocytes. Differentiation changes include the induction of phagocytosis, the initiation of nitroblue tetrazolium-reducing activity, and the appearance of nonspecific acid esterase. The authors have found that the 24-homo- and 26-homo-1,25-dihydroxyvitamin D/sub 3/ and their ..delta../sup 22/ analogues are 10-fold more potent than 1,25-dihydroxyvitamin D/sub 3/ in inducing differentiation of HL-60 cells in vitro. In vivo, these analogues show activity similar to 1,25-dihydroxy-vitamin D/sub 3/ in stimulating intestinal calcium transport in vitamin D-deficient rats. The 24-homoanalogues are significantly less active, whereas the 26-homo derivatives are more active than the natural hormone in mobilizing calcium from bone. This unusual activity pattern cannot be explained on the basis of the affinity of these analogues for the 1,25-dihydroxy-vitamin D/sub 3/ intracellular receptor: both 24-homo- and 26-homo-1,25-dihydroxyvitamin D/sub 3/ have the same effectiveness as 1,25-dihydroxyvitamin D/sub 3/ in displacing the tritiated hormone from its receptor in rat intestine of HL-60 cells. These analogues of 1,25-dihydroxyvitamin D/sub 3/ may be of some interest as possible therapeutic substances, or as tools in understanding the action of 1,25-dihydroxyvitamin D/sub 3/ in inducing differentiation.

• Research Organization: Univ. of Wisconsin, Madison
• OSTI ID: 5876116
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:9; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMAL CELLS
BIOLOGICAL EFFECTS
CELL DIFFERENTIATION
CHOLECALCIFEROL
DISEASES
DOSE-RESPONSE RELATIONSHIPS
HEMIC DISEASES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LEUKEMIA
MEMBRANES
MUCOUS MEMBRANES
NEOPLASMS
PHAGOCYTOSIS
RADIORECEPTOR ASSAY
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TUMOR CELLS
VITAMIN D
VITAMINS