Novel vitamin D analogs as potential therapeutics: Metabolism, toxicity profiling, and antiproliferative activity

Anticancer Research

Volumn 34, Issue 5, 2014, Pages 2153-2164

  Chen, Jianjun ^a,e   Wang, Jin ^a   Kim, Tae Kang ^b   Tieu, Elaine W ^d   Tang, Edith K Y ^d   Lin, Zongtao ^a   Kovacic, Dianne ^b   Miller, Duane D ^a   Postlethwaite, Arnold ^c   Tuckey, Robert C ^d   Slominski, Andrzej T ^b,c   Li, Wei ^a  

^a Department of Pharmaceutical Sciences   (India)

^b Department of Pathology and Laboratory Medicine Center for Cancer Research   (India)

^c UNIVERSITY OF TENNESSEE HEALTH SCIENCE CENTER   (United States)

^d UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^e USA   (United States)

Author keywords

20(OH)D3 analogs; Hypercalcemic effect; Liver microsomal stability; VDR translocation

Indexed keywords

1,20R DIHYDROXYVITAMIN D3; 1,20S DIHYDROXYVITAMIN D3; CYTOCHROME P450; UNCLASSIFIED DRUG; VITAMIN D DERIVATIVE; VITAMIN D RECEPTOR; ANTINEOPLASTIC AGENT; CALCITRIOL RECEPTOR; DRUG DERIVATIVE; VITAMIN D;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIPROLIFERATIVE ACTIVITY; ARTICLE; CELL NUCLEUS; CELL PROLIFERATION; CONTROLLED STUDY; CYTOPLASM; DRUG DESIGN; DRUG HALF LIFE; DRUG METABOLISM; DRUG POTENCY; DRUG SYNTHESIS; ENZYME METABOLISM; IN VITRO STUDY; IN VIVO STUDY; KERATINOCYTE; LIVER MICROSOME; MALE; MOUSE; NONHUMAN; STRUCTURE ACTIVITY RELATION; 20(OH)D3 ANALOGS; ANIMAL; DRUG EFFECT; HALF LIFE TIME; HYPERCALCEMIC EFFECT; LIVER MICROSOMAL STABILITY; METABOLISM; VDR TRANSLOCATION;

20(OH)D3 ANALOGS; HYPERCALCEMIC EFFECT; LIVER MICROSOMAL STABILITY; VDR TRANSLOCATION;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL PROLIFERATION; HALF-LIFE; MICE; MICROSOMES, LIVER; RECEPTORS, CALCITRIOL; VITAMIN D;

EID: 84902951389     PISSN: 02507005     EISSN: 17917530     Source Type: Journal    
DOI: None     Document Type: Article

References (41)

1. Pinette KV, Yee YK, Amegadzie BY and Nagpal S: Vitamin D receptor as a drug discovery target. Mini Rev Med Chem 3: 193-204, 2003.
2. Masuda S and Jones G: Promise of vitamin D analogues in the treatment of hyperproliferative conditions. Mol Cancer Ther 5: 797-808, 2006.
3. Slominski AT, Zmijewski MA, Semak I, Sweatman T, Janjetovic Z, Li W, Zjawiony JK and Tuckey RC: Sequential metabolism of 7-dehydrocholesterol to steroidal 5, 7-dienes in adrenal glands and its biological implication in the skin. PLoS One 4: e4309, 2009.
4. Slominski AT, Kim TK, Chen J, Nguyen MN, Li W, Yates CR, Sweatman T, Janjetovic Z and Tuckey RC: Cytochrome P450scc-dependent metabolism of 7-dehydrocholesterol in placenta and epidermal keratinocytes. Int J Biochem Cell Biol 44: 2003-2018, 2012.
5. Slominski A, Zjawiony J, Wortsman J, Semak I, Stewart J, Pisarchik A, Sweatman T, Marcos J, Dunbar CC and Tuckey RC: A novel pathway for sequential transformation of 7-dehydrocholesterol and expression of the P450scc system in mammalian skin. Eur J Biochem 271: 4178-4188, 2004.
6. Slominski A, Li W, Zbytek B, Tuckey RC, Zjawiony JK, Nguyen MN, Janjetovic Z, Zmijewski MA, Sweatman TW, Miller DD, Chen J and Postlethwaite AE: Enzymatic production or chemical synthesis and uses for 5, 7-dienes and UVB conversion products thereof. US Pat Appl Publ US 20110118228 A20110118221 20120110519, 2011.
7. Slominski A, Kim TK, Zmijewski MA, Janjetovic Z, Li W, Chen J, Kusniatsova EI, Semak I, Postlethwaite A, Miller DD, Zjawiony JK and Tuckey RC: Novel vitamin D photoproducts and their precursors in the skin. Dermatoendocrinol 5: 7-19, 2013.
8. 3-like derivatives. Photochem Photobiol Sci 7: 1570-1576, 2008.
9. Zmijewski MA, Li W, Zjawiony JK, Sweatman TW, Chen J, Miller DD and Slominski AT: Photo-conversion of two epimers (20R and 20S) of pregna-5, 7-diene-3beta, 17alpha, 20-triol and their bioactivity in melanoma cells. Steroids 74: 218-228, 2009.
10. Zmijewski MA, Li W, Chen J, Kim TK, Zjawiony JK, Sweatman TW, Miller DD and Slominski AT: Synthesis and photochemical transformation of 3beta, 21-dihydroxypregna-5, 7-dien-20-one to novel secosteroids that show anti-melanoma activity. Steroids 76: 193-203, 2011.
11. Slominski AT, Zmijewski MA, Semak I, Zbytek B, Pisarchik A, Li W, Zjawiony J and Tuckey RC: Cytochromes p450 and skin cancer: role of local endocrine pathways. Anticancer Agents Med Chem 14: 77-96, 2014.
12. Slominski AT, Kim TK, Li W, Yi AK, Postlethwaite A and Tuckey RC: The role of CYP11A1 in the production of vitamin D metabolites and their role in the regulation of epidermal functions. J Steroid Biochem Mol Biol 2013.
13. Slominski A, Semak I, Zjawiony J, Wortsman J, Li W, Szczesniewski A and Tuckey RC: The cytochrome P450scc system opens an alternate pathway of vitamin D3 metabolism. FEBS J 272: 4080-4090, 2005.
14. 3 by cytochrome P450scc. FEBS J 275: 2585-2596, 2008.
15. Tuckey RC, Li W, Shehabi HZ, Janjetovic Z, Nguyen MN, Kim TK, Chen J, Howell DE, Benson HA, Sweatman T, Baldisseri DM and Slominski A: Production of 22-hydroxy metabolites of vitamin d3 by cytochrome p450scc (CYP11A1) and analysis of their biological activities on skin cells. Drug Metab Dispos 39: 1577-1588, 2011.
16. 2 and 17, 20-dihydroxyvitamin D2. FEBS J 273: 2891-2901, 2006.
17. Nguyen MN, Slominski A, Li W, Ng YR and Tuckey RC: Metabolism of vitamin d2 to 17, 20, 24-trihydroxyvitamin d2 by cytochrome p450scc (CYP11A1). Drug Metab Dispos 37: 761-767, 2009.
18. 3 incorporated into phospholipid vesicles by human CYP27A1. J Steroid Biochem Mol Biol 129: 163-171, 2012.
19. Slominski AT, Kim TK, Shehabi HZ, Tang EK, Benson HA, Semak I, Lin Z, Yates CR, Wang J, Li W and Tuckey RC: In vivo production of novel vitamin D2 hydroxy-derivatives by human placentas, epidermal keratinocytes, Caco-2 colon cells and the adrenal gland. Mol Cell Endocrinol 383: 181-192, 2014.
20. 3 or 7-dehydrocholesterol metabolism by cytochrome P450scc show anti-leukemia effects, having low or absent calcemic activity. PLoS One 5: e9907, 2010.
21. 2 is a noncalcemic analog of vitamin D with potent antiproliferative and prodifferentiation activities in normal and malignant cells. Am J Physiol Cell Physiol 300: C526-541, 2011.
22. Kim T-K, Wang J, Janjetovic Z, Chen J, Tuckey RC, Nguyen MN, Tang EKY, Miller D, Li W and Slominski AT: Correlation between secosteroid induced vitamin D receptor activity in melanoma cells and computer-modeled receptor binding strength. Mol Cell Endocrinol 361: 143-152, 2012.
23. 3 hydroxylation by cytochrome P450scc, stimulates keratinocyte differentiation. J Invest Dermatol 128: 2271-2280, 2008.
24. 3 hydroxylation by P450scc, decreases NF-kappaB activity by increasing IkappaB alpha levels in human keratinocytes. PLoS One 4: e5988, 2009.
25. 3, novel P450scc product, stimulates differentiation and inhibits proliferation and NF-kappaB activity in human keratinocytes. J Cell Physiol 223: 36-48, 2010.
26. Slominski AT, Janjetovic Z, Kim TK, Wright AC, Grese LN, Riney SJ, Nguyen MN and Tuckey RC: Novel vitamin D hydroxyderivatives inhibit melanoma growth and show differential effects on normal melanocytes. Anticancer Res 32: 3733-3742, 2012.
27. 3, exhibits potent antifibrogenic activity in vivo. J Clin Endocrinol Metab 98: E298-303, 2013.
28. Slominski AT, Li W, Bhattacharya SK, Smith RA, Johnson PL, Chen J, Nelson KE, Tuckey RC, Miller D, Jiao Y, Gu W and Postlethwaite AE: Vitamin D analogs 17, 20S(OH)2pD and 17, 20R(OH)2pD are noncalcemic and exhibit antifibrotic activity. J Invest Dermatol 131: 1167-1169, 2011.
29. 3, which shows antiproliferative activity. Steroids 75: 926-935, 2010.
30. 3. J Med Chem 55: 3573-3577, 2012.
31. Chen J, Slominski AT, Miller DD and Li W: Effects of sidechain length and composition on the kinetic conversion and product distribution of vitamin D analogs determined by real-time NMR. Dermato-Endocrinology 5: 142-149, 2013.
32. Li CM, Chen J, Lu Y, Narayanan R, Parke DN, Li W, Ahn S, Miller DD and Dalton JT: Pharmacokinetic optimization of 4-substituted methoxybenzoyl-Aryl-thiazole and 2-Aryl-4-benzoyl-imidazole for improving oral bioavailability. Drug Metab Dispos 39: 1833-1839, 2011.
33. Slominski A, Zbytek B and Slominski R: Inhibitors of melanogenesis increase toxicity of cyclophosphamide and lymphocytes against melanoma cells. Int J Cancer 124: 1470-1477, 2009.
34. 3 metabolism by human and mouse CYP27B1. Drug Metab Dispos 41: 1112-1124, 2013.
35. 3 1alpha-hydroxylase (CYP27B1). J Steroid Biochem Mol Biol 119: 171-179, 2010.
36. Tieu EW, Tang EK, Chen J, Li W, Nguyen MN, Janjetovic Z, Slominski A and Tuckey RC: Rat CYP24A1 acts on 20-hydro-xyvitamin D(3) producing hydroxylated products with increased biological activity. Biochem Pharmacol 84: 1696-1704, 2012.
37. 3 analogues: disassociation of their prominent antileukemic effects from their lack of calcium modulation. Cancer Res 61: 3361-3368, 2001.
38. Odze RD, Goldblum JR and Crawford JM: Surgical pathology of the GI tract, liver, biliary tract, and pancreas. Philadelphia, PA: Saunders, 2004.
39. 3 metabolism by cytochrome P450scc (CYP11A1) in phospholipid vesicles and cyclodextrin. Int J Biochem Cell Biol 40: 2619-2626, 2008.
40. Brozyna AA, Jozwicki W, Janjetovic Z and Slominski AT: Expression of vitamin D receptor decreases during progression of pigmented skin lesions. Hum Pathol 42: 618-631, 2011.
41. Slominski AT and Carlson AJ: Melanoma resistance: bright future for academicians and challenge for patient advocates. Mayo Clinic Proceedings in press, 2014.