A novel vitamin D analog with two double bonds in its side chain: A potent inducer of osteoblastic cell differentiation

• Published in: Biochemical pharmacology Vol. 51; no. 7; pp. 887 - 892
• Main Authors: Mahonen, Anitta, Jääskeläinen, Tiina, Mäenpää, Pekka H.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 12.04.1996; Elsevier Science
• Subjects: alkaline phosphatase; analog; Antineoplastic agents; Antineoplastic Agents - pharmacology; Base Sequence; Biological and medical sciences; Calcitriol - analogs & derivatives; Calcitriol - pharmacology; Cell Differentiation - drug effects; Chemotherapy; differentiation; Humans; Medical sciences; Molecular Sequence Data; osteoblast; osteocalcin; Osteosarcoma - drug therapy; Pharmacology. Drug treatments; Time Factors; Tumor Cells, Cultured; vitamin D; Vitamin D - analogs & derivatives; Vitamin D - chemistry; differentiation; AP-1+VDRE; EB 1089; VDR; vitamin D; VDRE; osteoblast; RXR; analog; DMEM; OC; calcitriol; FCS; osteocalcin; alkaline phosphatase; Antineoplastic agent; Cell line; Vitamin D; Analog; Vitamin; Cell differentiation; In vitro; Biological activity
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/0006-2952(95)02242-2

EB 1089 (1α,25-dihydroxy-22,24-diene-24,26,27-trihomovitamin D 3) is a novel, synthetic analog of calcitriol, chatactetized by two extra double bonds in its side chain. It is less potent than calcitriol in its calcemic action, but is an order of magnitude more potent in its antiproliferative action. The aim of this study was to determine the ability of EB 1089 to induce the well-known biological effects of calcitriol in MG-63 human osteosarcoma cells (i.e. by inhibiting cell proliferation and by induction of differentiation). Both calcitriol and EB 1089 significantly decreased cell growth after 2 days in culture. At 5 days, however, EB 1089 was more potent than the natural hormone in inhibiting the proliferation of MG-63 cells. Potent effects of EB 1089 on cell differentiation were also seen in the stimulation of alkaline phosphatase activity, cellular vitamin D receptor mRNA levels, and medium osteocalcin synthesis. EB 1089 was clearly more effective than calcitriol in stimulating alkaline phosphatase activity and osteocalcin synthesis. In gel shift assays, the binding of vitamin D receptor to the composite AP-1 plus vitamin-D-responsive promoter region of the human osteocalcin gene after EB 1089 treatment was stronger and longer-lasting than after calcitriol treatment.