Metabolism of the vitamin D analog EB1089 by cultured human cells: Redirection of hydroxylation site to distal carbons of the side-chain

Biochemical Pharmacology

Volumn 53, Issue 6, 1997, Pages 783-793

  Shankar, V Narayanaswamy ^a   Dilworth, F Jeffrey ^a   Makin, Hugh L J ^b   Schroeder, Neil J ^b   Trafford, David J H ^b   Kissmeyer, Anne Marie ^c   Calverley, Martin J ^c   Binderup, Ernst ^c   Jonesr, Glenville ^a  

^a QUEEN S UNIVERSITY   (Canada)

^b QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

^c LEO PHARMA A S   (Denmark)

Author keywords

1,25 dihydroxyvitamin D3; calcitriol; cytochrome P450; EB1089; vitamin D analogs; vitamin D metabolism

Indexed keywords

CALCITRIOL; CYTOCHROME P450; KETOCONAZOLE; SEOCALCITOL; VITAMIN D DERIVATIVE;

ARTICLE; CELL CULTURE; CONTROLLED STUDY; DRUG METABOLISM; GAS CHROMATOGRAPHY; HEPATOMA CELL; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; HYDROXYLATION; IN VITRO STUDY; ISOTOPE LABELING; KERATINOCYTE; LIVER CELL; MASS SPECTROMETRY; PRIORITY JOURNAL; ULTRAVIOLET SPECTROPHOTOMETRY;

ANTINEOPLASTIC AGENTS; CALCITRIOL; CELLS, CULTURED; CYTOCHROME P-450 ENZYME SYSTEM; HUMANS; HYDROXYLATION; KERATINOCYTES; TRANSFECTION;

EID: 0001458751     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0006-2952(96)00815-5     Document Type: Article

References (30)

1. Shankar VN, Makin HLJ, Schroeder NJ, Trafford DJH, Kissmeyer A-M, Binderup E, Calverley MJ and Jones G, Metabolism of the antiproliferative vitamin D analogue, EB1089, in a cultured human keratinocyte model. Bone 17: 326 (Abst. P27), 1995.
2. Shankar VN, Makin HLJ, Schroeder NJ, Trafford DJH, Kissmeyer A-M, Binderup E, Calverley MJ and Jones G, Metabolism of vitamin D analogs containing side chain double bonds: conjugated system of EB1089 blocks 24-hydroxylation. J Bone Mineral Res 10: S389 (Abst. M548), 1995.
3. Suda T, Shinki T and Takahashi N, The role of vitamin D in bone and intestinal cell differentiation. Annu Rev Nutr 10: 195-211, 1990.
4. Calverley MJ, Synthesis of MC903, a biologically active vitamin D metabolite analogue. Tetrahedron 43: 4609-4619, 1987.
5. 3 with an oxygen atom in the side chain skeleton: a trial of the development of vitamin D compounds which exhibit potent differentiation activation activity without inducing hypercalcemia. FEBS Lett 226: 58-62, 1987.
6. 3 Gene Regulation, Structure Function Analysis and Clinical Applications, Proceedings of the Eighth Workshop on Vitamin D, Paris, France, 5-10 July 1991. (Eds. Norman AW, Bouillon R and Thomasset M), pp. 159-162, Walter de Gruyter, Berlin, 1991.
7. 3 is due to reduced catabolism and altered protein binding. Biochem Pharmacol 47: 987-993, 1994.
8. 3 in osteosarcoma cell line UMR-106. J Biol Chem 262: 14394-14401, 1987.
9. Akiyoshi-Shibata M, Sakaki T, Ohyama Y, Noshiro M, Okuda K and Yabusaki Y, Further oxidation of hydroxycalcidiol by calcidiol 24-hydroxylase - A study with the mature enzyme expressed in Escherichia coli. EurJ Biochem 224: 335-343, 1994.
10. 3 Gene Regulation, Structure Function Analysis and Clinical Applications, Proceedings of the Eighth Workshop on Vitamin D, Paris, France, 5-10 July 1991. (Eds. Norman AW, Bouillion R and Thomasset M), pp. 192-193, Walter de Gruyter, Berlin, 1991.
11. Mathiasen IS, Colston KW and Binderup L, EB1089, a novel vitamin D analogue has strong antiproliferative and differentiation-inducing effects on cancer cells. J Steroid Biochem Molec Biol 46: 365-371, 1993.
12. James SY, Mackay AC, Binderup L and Colston KW, Effects of a new synthetic analogue, EB1089, on the oestrogenresponsive growth of human breast cancer cells. J Endocr 141 : 555-563, 1994.
13. Masuda S, Strugnell S, Calverley M, Makin HLJ, Kremer R and Jones G, In vitro metabolism of the anti-psoriatic vitamin D analog, calcipotriol, in two cultured human keratinocyte models. J Biol Chem 269: 4794-4803, 1994.
14. 3 to calcitroic acid. Biochem J 262: 173-180, 1989.
15. Henderson J, Sebag M, Rhim J, Goltzman D and Kremer R, Dysregulation of parathyroid hormone-like peptide expression and secretion in a keratinocyte model of tumour progression. Cancer Res 51: 6521-6528, 1991.
16. 3 in a keratinocyte model or tumour progression. J Biol Chem 267: 12162-12167, 1992.
17. Bligh EG and Dyer WJ, A rapid method of total lipid extraction and purification. Can J Biochem 37: 911-917, 1957.
18. Qaw F, Calverley MJ, Schroeder NJ, Trafford DJH, Makin HLJ and Jones G, In vivo metabolism of the vitamin D analog, dihydrotachysterol. J Biol Chem 268: 282-292, 1993.
19. Sambrook J, Fritsch EF and Maniatis T, In: Molecular Cloning: a Laboratory Manual. 2nd Ed, pp. 16.42-16.44. Cold Spring Harbor Laboratories, Cold Spring Harbor, NY, 1989.
20. Guo Y, Strugnell S, Back D and Jones G, Transfected human liver cytochrome P450 hydroxylates vitamin D analogs at different side-chain positions. Proc Natl Acad Sci USA 90: 8668-8672, 1993.
21. 3 24-hydroxylase. FEBS Lett 278: 195-198, 1991.
22. Dilworth FJ, Scott I, Green A, Strugnell S, Guo Y-D, Roberts EA, Kremer R, Calverley MJ, Makin HLJ and Jones G, Different mechanisms of hydroxylation site selection by liver and kidney cytochrome P-450 species (CYP27 and CYP24) involved in vitamin D metabolism. J Biol Chem 270: 16766-16774, 1995.
23. Makin HLJ, Jones G and Calverley MJ, Analysis of Vitamin D, its metabolites and structural analogues. In: Steroid Analysis (Eds. Makin HLJ, Cower DB and Kirk DN), pp. 562-620. Blackie, Glasgow, 1995.
24. Kissmeyer A-M, Binderup E, Binderup L, Hansen CM, Rastrup-Andersen N, Makin HLJ, Shankar VN and Jones G, The metabolism of the vitamin D analog EB1089: Identification of in vivo and in vitro liver metabolites and their biological activities. Biochem Pharmacol 53: 000-000; 1997.
25. 3-26,23-lactone. J Biol Chem 259: 884-889, 1984.
26. 3,-26,23-lactone. Arch Biochem Biophys 242: 82-89, 1985.
27. 3-24-hydroxylase. J Bone Mineral Res 10: 1951-1958, 1995.
28. 3 side chain. J Bone Mineral Res 10: S388 (Abst. M546), 1995.
29. Kissmeyer A-M, Shankar VN, Jones G and Makin HLJ, The in vitro and in vivo metabolism of EB1089. Bone 17: S327 (Abst. P29), 1995.
30. 3 (VD) analogues MC903, EB1089, and KH1060 activate the VD receptor: homodimers show higher ligand sensitivity than heterodimers with retinoid X receptors. J Steroid Biochem Molec Biol 51: 137-142, 1994.