Skip to main content
SpringerLink
Log in

Vitamin D Analogs and Breast Cancer

  • Conference paper
Vitamin D Analogs in Cancer Prevention and Therapy

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 164))

Abstract

Breast cancer is the most frequent malignancy of women in the Western world. Vitamin D compounds constitute a novel alternative to the conventional use of antiestrogens for chemoprevention and chemotherapy. The biologically active form of vitamin D, 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3], not only plays an essential role in the control of calcium homeostasis, but also acts on cells of a variety of tissues to promote inhibition of cellular proliferation and induction of differentiation. The potential use of 1,25(OH)2D3in the treatment of cancer is limited by its propensity to cause hypercalcemia at pharmacologically active doses. This has led to the synthesis of analogs of vitamin D that exhibit potent anticancer effects, but have low calcemic activity. Evidence from both in vitro and in vivo studies has demonstrated that vitamin D compounds can inhibit the growth of breast cancer cells, suggesting their therapeutic value in the treatment or prevention of this disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abe J, Nakano T, Nishii Y, Matsumoto T, Ogata E, Ikeda K (1991) A novel vitamin D3 analog, 22-oxa-1,25-dihydroxyvitamin D3, inhibits the growth of human breast cancer in vitro and in vivo without causing hypercalcemia. Endocrinology 129:832–837

    Article  PubMed  CAS  Google Scholar 

  • Abe-Hashimoto J, Kikuchi T, Matsumoto T, Nishii Y, Ogata E, Ikeda K (1993) Antitumor effect of 22-oxa-calcitriol, a noncalcemic analogue of calcitriol, in athymic mice implanted with human breast carcinoma and its synergism with tamoxifen. Cancer Res 53:2534–2537

    PubMed  CAS  Google Scholar 

  • Binderup L, Latini S, Binderup E, Bretting C, Calverley M, Hansen K (1991) 20-epi-vitamin D3 analogues: a novel class of potent regulators of cell growth and immune responses. Biochem Pharmacol 42:1569–1575

    Article  PubMed  CAS  Google Scholar 

  • Bouillon R, Okamura WH and Norman AW (1995) Structure-function relationships in the vitamin D endocrine system. Endocrine Rev 16:200–257 Buras RR, Schumaker LM, Davoodi F, Brenner RV, Shabahang M, Nauta RJ, Evans SR (1994) Vitamin D receptors in breast cancer cells. Breast Cancer Res Treat 31:191–202

    Google Scholar 

  • Campbell MJ, Elstner E, Holden S, Uskokovic M, Koeffler HP (1997a) Inhibition of prostate cancer cells by 19-nor-hexafluride vitamin D3 analogues correlates with their induction of p21waf1, p27kip1 and E-cadherin. J Mol Endocrinol 19:15–27

    Article  CAS  Google Scholar 

  • Campbell MJ, Reddy GS, Koeffler HP (1997b) Vitamin D3 analogs and their 24-oxo metabolites equally inhibit clonal proliferation of a variety of cancer cells but have different molecular effects. J Cell Biochem 66:413–425

    Article  CAS  Google Scholar 

  • Campbell MJ, Gombart AF, Kwok SH, Koeffler HP (2000) The anti-proliferative effects of 1a,25(OH)2D3on breast and prostate cancer cells are associated with induction of BRCA1 gene expression. Oncogene 19:5091–5097

    Article  PubMed  CAS  Google Scholar 

  • Carlberg C, Mathiasen YS, Binderup L (1995) The 1,25-dihydroxyvitamin D3 (VD) analog MC903, EB1089 and KH1060 activate the VD receptor: homodimers show higher ligand sensitivity than heterodimers with retinoid x receptors. J Steroid Biochem Molecular Biol 51:137–142

    Article  Google Scholar 

  • Chouvet C, Vicard E, Devonec M, Saez S (1986) 1,25-Dihydroxyvitamin D3 inhibitory effect on the growth of two human breast cancer cell lines (MCF-7, BT-20). J Steroid Biochem 24: 373–376

    Article  PubMed  CAS  Google Scholar 

  • Colston KW, Berger U, Coombes RC (1989) Possible role for vitamin D in controlling breast cancer cell proliferation. Lancet 1:188–191

    Article  PubMed  CAS  Google Scholar 

  • Colston KW, Chander SK, Mackay AG, Coombes RC (1992a) Effects of synthetic vitamin D analogues on breast cancer cell proliferation in vivo and in vitro. Biochem Pharmacol 44:693–702

    Article  CAS  Google Scholar 

  • Colston KW, Mackey AG, James SY, Binderup L, Chander S, Coombes RC (1992b) EB1089: a new vitamin D analog that inhibits the growth of breast cancer cells (in vivo) and (in vitro). Biochem Pharmacol 44:2273–2280

    Article  CAS  Google Scholar 

  • Colston KW, Perks CM, Xie SP, Holly JM (1998) Growth inhibition of both MCF-7 and Hs578T human breast cancer cell lines by vitamin D analogues is associated with increased expression of insulin-like growth factor binding protein-3. J Mol Endocrinol 20:157–162

    Article  PubMed  CAS  Google Scholar 

  • Danielsson C, Mathiasen IS, James SY, Nayeri S, Bretting C, Hansen CM, Colston KW, Carlberg C (1997) Sensitive induction of apoptosis in breast cancer cells by a novel 1,25-dihydroxyvitamin D3 analogue shows relation to promoter selectivity. J Cell Biochem 66:552–562

    Article  PubMed  CAS  Google Scholar 

  • De Vos S, Holden S, Heber D, Elstner E, Binderup L, Usokovic M, Rude B, Chen DL, Cho SK, Koeffler HP (1997) (In vitro) effects of potent vitamin D3 analogs on clonal proliferation of human prostate cancer cell lines. Prostate 87:424–430

    Google Scholar 

  • Demirpence E, Balaguer P, Trousse F, Nicolas JC, Pons M, Gagne D (1994) Antiestrogenic effects of all-trans-retinoic acid and 1,25-dihydroxyvitamin D3 in breast cancer cells occur at the estrogen response element level but through different molecular mechanisms. Cancer Res 54:1458–1464

    PubMed  CAS  Google Scholar 

  • Dilworth FJ, Calverley MJ, Makin HL, Jones G (1994) Increased biological activity of 20-epi-1,25-dihydroxyvitamin D3 is due to reduced catabolism and altered protein binding. Biochem Pharmacol 47:987–993

    Article  PubMed  CAS  Google Scholar 

  • Eisman JA, Martin TJ, MacIntyre I, Moseley JM (1979) 1,25-dihydroxyvitamin-D-receptor in breast cancer cells. Lancet 2:1335–1336

    Article  PubMed  CAS  Google Scholar 

  • Eisman JA, Martin TJ, MacIntyre I (1980) Presence of 1,25-dihydroxyvitamin D receptor in normal and abnormal breast tissue. Prog Biochem Pharmacol 17:143–150

    PubMed  CAS  Google Scholar 

  • Eisman JA, Barkla DH, Tutton PJ (1987) Suppression of in vivo growth of human cancer solid tumor xenografts by 1,25-dihydroxyvitamin D3. Cancer Res 47:21–25

    PubMed  CAS  Google Scholar 

  • Elstner E, Lee YY, Hasiya M, Pakkala S, Binderup L, Norman AW, Okamura WH, Koeffler HP (1994) 1,25-dihydroxy-20-epi-vitamin D3: an extraordinary potent inhibitor of leukemia cell growth (in vitro). Blood 84:1960–1968

    PubMed  CAS  Google Scholar 

  • Elstner E, Linker-Israeli M, Said J, Umiel T, De Vos S, Shintaku IP, Heber D, Binderup LC, Usokovic M, Koeffler HP (1995) 20-epi-vitamin D3 analogs: a novel class of potent inhibitors of proliferation and inducers of differentiation of human breast cell lines. Cancer Res 55:2822–2830

    PubMed  CAS  Google Scholar 

  • Elstner E, Linker-Israeli M, Le J, Grillier I, Said J, Shintaku IP, Krajewski S, Reed JC, Binderup L, Koeffler HP (1996) Combination of potent 20-epi-vitamin D3 (KH1060) and 9-cis-retinoic acid inhibits irreversible clonal growth, decreases bcl-2 expression and induces apoptosis in HL-60 leukemic cells. Cancer Res 55:2822–2830

    Google Scholar 

  • Elstner E, Linker-Israeli M, Le J, Umiel T, Michl P, Said JW, Binderup L, Rreed JC, Koeffler HP (1997) Synergistic decrease of clonal proliferation, induction of differentiation, and apoptosis of acute promyelocytic leukemia cells after combined treatment with novel 20-epi-vitamin D3 analogs and 9-cis retinoic acid. J Clinical Invest 99:1–12

    Article  Google Scholar 

  • Elstner E, Campbell MJ, Munker R, Shintaku P, Binderup L, Heber D, Said J, Koeffler HP (1999) Novel 20-epi-vitamin D3 analog: combined with 9-cis-retinoic acid markedly inhibits colony growth of prostate cancer cells. Prostate 40:141–149

    Article  PubMed  CAS  Google Scholar 

  • Evans RM (1988) The steroid and thyroid hormone receptor superfamily. Science 240:889–895

    Article  PubMed  CAS  Google Scholar 

  • Evans TR, Colston KW, Lofts FJ, Cunningham D, Anthoney DA, Gogas H, de Bono JS, Hamberg KJ, Skov T, Manis JL (2002) A phase II trial of the vitamin D analogue Seocalcitol (EB1089) in patients with inoperable pancreatic cancer. Br J Cancer 86:680–685

    Article  PubMed  CAS  Google Scholar 

  • Falette N, Frappart L, Lefebvre MF, Saez S (1989) Increased epidermal growth factor receptor level in breast cancer cells treated by 1,25-dihydroxyvitamin D3. Mol Cell Endocrinol 63:189–198

    Article  PubMed  CAS  Google Scholar 

  • Findlay DM, Michelangeli VP, Eisman JA, Frampton RJ, Moseley JM, MacIntyre I, Whitehead T, Martin TJ (1980) Calcitonin and 1,25-dihydroxyvitamin D3 receptors in human breast cancer cell lines. Cancer Res 40:4764–4767

    PubMed  CAS  Google Scholar 

  • Frampton RJ, Omond SA, Eisman JA (1983) Inhibition of human cancer cell growth by 1,25-dihydroxyvitamin D3 metabolites. Cancer Res 43:4443–4447

    PubMed  CAS  Google Scholar 

  • Gallo MA, Kaufman D (1997) Antagonistic and agonistic effects of tamoxifen: significance in human cancer. Semin Oncol 24:S1–71-S1–80

    PubMed  CAS  Google Scholar 

  • Gert-Jan CM, van den Bemd HA, Pols JC, Kirkenhager JC (1996) Conformational change and enhanced stabilization of the vitamin D receptor by the 1,25-dihydroxyvitamin D3 analog KH1060. Proc Natl Acad Sci U S A 93:10685–10690

    Article  Google Scholar 

  • Grese TA, Sluka JP, Bryant Hu, Cullinan GJ, Glasebook AL, Jones CD, Palkowitz AD, Sato M, Termine JD, Winter MA, Yang NN, Godge JA (1997) A molecular determinant of tissue selectivity in estrogen receptor modulators. Proc Nat Acad Sci U S A 94:14105–14110

    Article  CAS  Google Scholar 

  • Gulliford T, English J, Colston KW, Menday P, Moller S, Coombes RC (1998) A phase I study of the vitamin D analogue EB1089 in patients with advanced breast and colorectal cancer. Br J Cancer 78:6–13

    Article  PubMed  CAS  Google Scholar 

  • Hansen CM, Danielsson C, Carlberg C (1996) The potent anti-proliferative effect of 20-epianalogues of the 1,25 dihydroxyvitamin D3 in human breast-cancer MCF-7 cells is related to promoter selectivity. Int J Cancer 67:739–742

    Article  CAS  Google Scholar 

  • Hermanson O, Glass CK, Rosenfeld MG (2002) Nuclear receptor coregulators: multiple modes of modification. Trends Endocrinol Metab 13:55–60

    Article  PubMed  CAS  Google Scholar 

  • Hisatake JH, Kubota T, Hisatake Y, Uskokovic M, Tomoyasu S, Koeffler HP (1999) 5,6-trans-16-ene-vitamin D3: a new class of potent inhibitors of proliferation of prostate, breast, and myeloid leukemic cells. Cancer Res 59:4023–4029

    PubMed  CAS  Google Scholar 

  • Hisatake J, O_Kelly J, Uskokovic M, Tomayasu S, Koeffler HP (2001) Novel vitamin D3 analog, 21-(3-methyl-3-hydroxy-butyl)-19-nor-D3, that modulates cell growth, differentiation, apoptosis, cell cycle, and induction of PTEN in leukemic cells. Blood 97:2427–2433

    Article  PubMed  CAS  Google Scholar 

  • Honda A, Nakashima N, Mori Y, Katsumata T, Ishizuka S (1992) Effects of vitamin D-binding proteins on HL-60 cell differentiation induced by 26,26,26,27,27,27,-hexafluoro-1 alpha, 25,dihydroxyvitamin D. J Steroid Biochem Mol Biol 41:109–112

    Article  PubMed  CAS  Google Scholar 

  • Horwitz KB, Jackson TA, Bain DL, Richer JK, Takimoto GS, Tung L (1996) Nuclear receptor coactivators and corepressors. Mol Endocrinol 10:1167–1177

    Article  PubMed  CAS  Google Scholar 

  • Imai Y, Pike JW, Koeffler HP (1995) Potent vitamin D3 analogs: their abilities to enhance transactivation and to bind the vitamin D3 response element. Leukemia Res 19:147–158

    Article  CAS  Google Scholar 

  • James SY, Mackay AG, Binderup L, Colston KW (1994) Effects of a new synthetic vitamin D analog, EB1089, on the estrogen responsive growth of human breast cancer cells. J Endocrinol 141:555–563

    Article  PubMed  CAS  Google Scholar 

  • James SY, Mackay AG, Colston KW (1996) Effects of 1,25 dihydroxyvitamin D3 and its analogues on induction of apoptosis in breast cancer cells. J Steroid Biochem Mol Biol 58:395–401

    Article  PubMed  CAS  Google Scholar 

  • Jensen SS, Madsen MW, Lukas J, Binderup L, Bartek J (2001) Inhibitory effects of 1alpha,25-dihydroxyvitamin D(3) on the G(1)-S phase-controlling machinery. Mol Endocrinol 15:1370–1380

    Article  PubMed  CAS  Google Scholar 

  • Jones G, Schnoes HK, DeLuca HF (1975) Isolation and identification of 1,25-dihydroxyvitamin D2. Biochemistry 14:1250–1256

    Article  PubMed  CAS  Google Scholar 

  • Jung SJ, Lee YY, Pakkala S, de Vos S, Elsner E, Norman AW, Green J, Uskokovic M, Koeffler HP (1996) 1,25-(OH)2–16-ene-vitamin D3 is a potent antileukemic agent with low potential to cause hypercalcemia. Leuk Res 18:453–463

    Article  Google Scholar 

  • Koeffler HP, Amatruda T, Ikekawa N, Kabayashi T, DeLuca HF (1984) Induction of macrophage differentiation of normal and leukemic myeloid stem cells by 1,25-dihydroxyvitamin D3 and its fluorinated analogues. Cancer Res 44:5624–5628

    PubMed  CAS  Google Scholar 

  • Koeffler HP, Bishop J, Reichel H, Singer F, Nagler A, Tobler A, Walker M, Norman AW (1990) Lymphocyte cell lines from vitamin D-dependent rickets type II show functional defects in the 1 alpha,25-dihydroxyvitamin D3 receptor. Mol Cell Endocrinol 70:1–11

    Article  PubMed  CAS  Google Scholar 

  • Koike M, Elstner E, Campbell MJ, Asou H, Uskokovic M, Tsuruoka N, Koeffler HP (1997) 19-nor-hexafluoride analogue of vitamin D3: a novel class of potent inhibitors of proliferation of human breast cell lines. Cancer Res 57:4545–4550

    PubMed  CAS  Google Scholar 

  • Koike M, Koshisuzuka K, Sawabata H, Yang R, Taub HE, Said J, Uskokovic M, Tsuruoka N, Koeffler HP (1999) 20-Cyclopropyl-cholecalciferol vitamin D3 analogs: a unique class of potent inhibitors of proliferation of human prostate, breast, and myeloid leukemia cell lines. Anticancer Res 19:1689–1698

    PubMed  CAS  Google Scholar 

  • Koshizuka K, Koike M, Asou H, Cho SK, Stephen T, Rude RK, Binderup L, Uskokovic M, Koeffler HP (1999a) Combined effects of vitamin D3 analogs and paclitaxel on the growth of MCF-7 breast cancer cells (in vivo). Breast Cancer Res Treat 53:113–120

    Article  CAS  Google Scholar 

  • Koshizuka K, Kubota T, Said J, Koike M, Binderup L, Uskokovic M, Koeffler HP (1999b) Combination therapy of a vitamin D3 analog and all trans retinoic acid: effect on human breast cancer in nude mice. Anticancer Res 19:519–524

    CAS  Google Scholar 

  • Kragballe K, Gjertsen BT, De Hoop D, Karlsmark T, van de Kerkhof PC, Larko O, Nieboer C, Roed-Petersen J, Strand A, Tikjob G (1991) Double-blind, right/left comparison of calcipotriol and betamethasone valerate in treatment of psoriasis vulgaris. Lancet 337:193–196

    Article  PubMed  CAS  Google Scholar 

  • Lazzaro G, Agadir A, Qing W, Poria M, Mehta RR, Moriarty RM, Das Gupta TK, Zhang XK, Mehta RG (2000) Induction of differentiation by 1alpha-hydroxyvitamin D(5) in T47D human breast cancer cells and its interaction with vitamin D receptors. Eur J Cancer 36:780–786

    Article  PubMed  CAS  Google Scholar 

  • Lee YY, Kim ES, Seol JG, Kim BK, Binderup L, Elstner E, Park DJ, Koeffler HP (1996) Effect of a vitamin D3 analog, EB1089, on hematopoietic stem cells from normal and myeloid leukemic blasts. Leukemia 10:1751–1757

    PubMed  CAS  Google Scholar 

  • Levy Y, Knutson JC, Bishop C, Shany S (1998) The novel analog 1,24(S)-dihydroxyvitamin D2 is as equipotent as 1,25-dihydroxyvitamin D3 in growth regulation of cancer cell lines. Anticancer Res 18:1769–1775

    PubMed  CAS  Google Scholar 

  • Liu W, Asa SL, Fantus G, Walfish PG, Ezzat S (2002) Vitamin D arrests thyroid carcinoma cell growth and induces p27 dephosphorylation and accumulation through PTEN/Akt-dependent and -independent pathways. Am J Pathol 160:511–519

    Article  PubMed  CAS  Google Scholar 

  • Love-Schimenti CD, Gibson DF, Ratnam AV, Bikle DD (1996) Antiestrogen potentiation of antiproliferative effects of vitamin D3 analogues in breast cancer cells. Cancer Res 56:2789–2794

    PubMed  CAS  Google Scholar 

  • Mathiasen IS, Colston KW, Binderup L (1993) EB1089, a novel vitamin D analog, has strong antiproliferative and differentiation inducing effects on cancer cells. J Steroid Biochem Molecular Biol 46:365–371

    Article  CAS  Google Scholar 

  • Mathiasen IS, Lademann U, Jaattela M (1999) Apoptosis induced by vitamin D compounds in breast cancer cells is inhibited by Bcl-2 but does not involve known caspases or p53. Cancer Res 59:4848–4856

    PubMed  CAS  Google Scholar 

  • Mathiasen IS, Hansen CM, Foghsgaard L, Jaattela M (2001) Sensitization to TNF-induced apoptosis by 1,25-dihydroxy vitamin D(3) involves up-regulation of the TNF receptor 1 and cathepsin B Int J Cancer 93:224–231

    CAS  Google Scholar 

  • Matsumoto H, Iino Y, Koibuchi Y, Andoh T, Horii Y, Takei H, Horiguchi J, Maemura M, Yokoe T, Morishita Y (1999) Antitumor effect of 22-oxacalcitriol on estrogen receptornegative MDA-MB-231 tumors in athymic mice. Oncol Rep 6:349–352

    PubMed  CAS  Google Scholar 

  • Maynard DF, Trankle WG, Norman AW, Okamura WH (1994) 14-epi stereoisomers of 25-hydroxy-and 1 alpha,25-dihydroxyvitamin D3: synthesis, isomerization to previtamins, and biological studies. J Med Chem 37:2387–2393

    Article  PubMed  CAS  Google Scholar 

  • Mehta RG, Moriarty RM, Mehta RR, Penmasta R, Lazzaro G, Constantinou A, Guo L (1997) Prevention of preneoplastic mammary lesion development by a novel vitamin D analogue, 1alpha-hydroxyvitamin D5. J Natl Cancer Inst 89:212–218

    Article  PubMed  CAS  Google Scholar 

  • Mehta RR, Bratescu L, Graves JM, Green A, Mehta RG (2000a) Differentiation of human breast carcinoma cells by a novel vitamin D analog: 1 alpha-hydroxyvitamin D5. Int J Oncol 16:65–73

    CAS  Google Scholar 

  • Mehta R, Hawthorne M, Uselding L, Albinescu D, Moriarty R, Christov K, Mehta R (2000b) Prevention of N-methyl-N-nitrosourea-induced mammary carcinogenesis in rats by 1alpha hydroxyvitamin D(5). J Natl Cancer Inst 92:1836–1840

    Article  CAS  Google Scholar 

  • Midland MM, Plumet Y, Okamur, WH (1993) Effects of C20 stereochemistry on the conformational profile of the side chains of vitamin D analogs. Bio Med Chem 3:1799–1804

    Article  CAS  Google Scholar 

  • Miller GJ, Stapleton GE, Ferrara JA, Lucia MS, Pfister S, Hedlund TE, Upadhya P (1992) The human prostatic carcinoma cell line LNCaP expresses biologically active, specific receptors for 1,25-dihydroxyvitamin D3. Cancer Res 52:515–520

    PubMed  CAS  Google Scholar 

  • Narvaez CJ, Welsh J (2001) Role of mitochondria and caspases in vitamin D-mediated apoptosis of MCF-7 breast cancer cells. J Biol Chem 276:9101–9107

    Article  PubMed  CAS  Google Scholar 

  • Nayeri S, Danielsson C, Kahlen J-P, Schr_der M, Mathiasen IS, Binderup L, Carlberg C (1995) The anti-proliferative effect of vitamin D3 analogues is not related to the AP-1 pathway, but related to promoter selectivity. Oncogene 11:1853–1858

    PubMed  CAS  Google Scholar 

  • Norman AW, Manchand PS, Uskokovic MR, Okamura WH, Takeuchi JA, Bishop JE, Hisatake JI, Koeffler HP, Peleg S (2000) Characterization of a novel analogue of 1alpha,25(OH)(2)-vitamin D(3) with two side chains: interaction with its nuclear receptor and cellular actions. J Med Chem 43:2719–2730

    Article  PubMed  CAS  Google Scholar 

  • O_Kelly J, Hisatake J, Hisatake Y, Bishop J, Norman A, Koeffler HP (2002) Normal myelopoiesis but abnormal T lymphocyte responses in vitamin D receptor knockout mice. J Clinical Invest 109:1091–1099

    CAS  Google Scholar 

  • Park WH, Seol JG, Kim ES, Hyun JM, Jung CW, Lee CC, Binderup L, Koeffler HP, Kim BK, Lee YY (2000) Induction of apoptosis by vitamin D3 analogue EB1089 in NCIH929 myeloma cells via activation of caspase 3 and p38 MAP kinase. Br J Haematol 109:576–583

    Article  PubMed  CAS  Google Scholar 

  • Peleg S, Sastry M, Collins ED, Bishop YE, Norman AW (1995) Distinct conformational changes induced by the 20-epi analogs of 1a, 25-dihydroxyvitamin D3 are associated with enhanced activation of the vitamin D receptor. J Biol Chem 270:10551–10558

    Article  PubMed  CAS  Google Scholar 

  • Pirianov G, Colston KW (2001) Interaction of vitamin D analogs with signaling pathways leading to active cell death in breast cancer cells. Steroids 66:309–318

    Article  PubMed  CAS  Google Scholar 

  • Pirianov G, Danielsson C, Carlberg C, James SY, Colston KW (1995) Potentiation by vitamin D analogs of TNFalpha and ceramide-induced apoptosis in MCF-7 cells is associated with activation of cytosolic phospholipase A2. Cell Death Differ 6:890–901

    Article  Google Scholar 

  • Rocker D, Ravid A, Liberman UA, Garach-Jehoshua O, Koren R (1994) 1,25-Dihydroxyvitamin D3 potentiates the cytotoxic effect of TNF on human breast cancer cells. Mol Cell Endocrinol 106:157–162

    Article  PubMed  CAS  Google Scholar 

  • Rozen F, Pollak M (1999) Inhibition of insulin-like growth factor I receptor signaling by the vitamin D analogue EB1089 in MCF-7 breast cancer cells: a role for insulin-like growth factor binding proteins. Int J Oncol 15:589–594

    PubMed  CAS  Google Scholar 

  • Rozen F, Yang XF, Huynh H, Pollak M (1997) Antiproliferative action of vitamin D-related compounds and insulin-like growth factor-binding protein 5 accumulation. J Natl Cancer Inst 89:652–656

    Article  PubMed  CAS  Google Scholar 

  • Saez S, Falette N, Guillot C, Meggouh F, Lefebvre MF, Crepin M (1993) William L. McGuire Memorial Symposium. 1,25(OH)2D3modulation of mammary tumor cell growth in vitro and in vivo. Breast Cancer Res Treat 27:69–81

    Article  PubMed  CAS  Google Scholar 

  • Shiohara M, Uskokovic M, Hisitake J, Hisatake Y, Koike K, Komiyama A, Koeffler HP (2001) 24-oxo metabolites of vitamin D3 analogues: disassociation of their prominent antileukemic effects from their lack of calcium modulation. Cancer Res 61:3361–3368

    PubMed  CAS  Google Scholar 

  • Simboli-Campbell M, Narvaez CJ, Tenniswood M, Welsh J (1996) 1,25-Dihydroxyvitamin D3 induces morphological and biochemical markers of apoptosis in MCF-7 breast cancer cells. J Steroid Biochem Mol Biol 58:367–376

    Article  PubMed  CAS  Google Scholar 

  • Simboli-Campbell M, Narvaez CJ, van Weelden K, Tenniswood M, Welsh J (1997) Comparative effects of 1,25(OH)2D3and EB1089 on cell cycle kinetics and apoptosis in MCF-7 breast cancer cells. Breast Cancer Res Treat 42:31–41

    Article  PubMed  CAS  Google Scholar 

  • Sjoden G, Smith C, Lindgren U, DeLuca HF (1985) 1 alpha-Hydroxyvitamin D2 is less toxic than 1 alpha-hydroxyvitamin D3 in the rat. Proc Soc Exp Biol Med 178:432–436

    PubMed  CAS  Google Scholar 

  • Skowronski RJ, Peehl DM, Feldman D (2000) Vitamin D and prostate cancer: 1,25-dihydroxyvitamin D3 receptors and actions in human prostate cancer cell lines. Endocrinology 132:1952–1960

    Article  Google Scholar 

  • Smith DC, Johnson CS, Freeman CC, Muindi J, Wilson JW, Trump DL (1999) A Phase I trial of calcitriol (1,25-dihydroxycholecalciferol) in patients with advanced malignancy. Clin Cancer Res 5:1339–1345

    PubMed  CAS  Google Scholar 

  • Sundaram S, Gewirtz DA (1999) The vitamin D3 analog EB 1089 enhances the response of human breast tumor cells to radiation. Radiat Res 152:479–486

    Article  PubMed  CAS  Google Scholar 

  • Sundaram S, Chaudhry M, Reardon D, Gupta M, Gewirtz DA (2000) The vitamin D3 analog EB 1089 enhances the antiproliferative and apoptotic effects of adriamycin in MCF-7 breast tumor cells. Breast Cancer Res Treat 63:1–10

    Article  PubMed  CAS  Google Scholar 

  • Swami S, Krishnan AV, Feldman D (2000) 1alpha,25-Dihydroxyvitamin D3 down-regulates estrogen receptor abundance and suppresses estrogen actions in MCF-7 human breast cancer cells. Clin Cancer Res 6:3371–3379

    PubMed  CAS  Google Scholar 

  • Tocchini-Valentini G, Rochel N, Wurtz JM, Moras D (2001) Crystal structures of the vitamin D receptor complexed to superagonist 20-epi ligands. Proc Natl Acad Sci USA 98:5491–5496

    Article  PubMed  CAS  Google Scholar 

  • Uskokovic MR, Stuzinski GP, Gardner JP, Reddy SG, Campbell MJ, Koeffler HP (1997) The 16-ene vitamin D analogs. Curr Pharm Design 3:99–123

    CAS  Google Scholar 

  • Vandewalle B, Hornez L, Wattez N, Revillion F, Lefebvre J (1995) Vitamin-D3 derivatives and breast-tumor cell growth: effect on intracellular calcium and apoptosis. Int J Cancer 61:806–811

    Article  PubMed  CAS  Google Scholar 

  • Verlinden L, Verstuyf A, Van Camp M, Marcelis S, Sabbe K, Zhao XY, Clercq PD, Vandewalle M, Bouillon R (2000) Two novel 14-epi-analogues of 1,25-dihydroxyvitamin D3 inhibit the growth of human breast cancer cells in vitro and in vivo. Cancer Res 60:2673–2679

    PubMed  CAS  Google Scholar 

  • Vink-van Wijngaarden T, Pols HA, Buurman CJ, Birkenhager JC, van Leeuwen JP (1994a) Combined effects of 1,25-dihydroxyvitamin D3 and tamoxifen on the growth of MCF-7 and ZR-75–1 human breast cancer cells. Breast Cancer Res Treat 29:161–168

    Article  CAS  Google Scholar 

  • Vink-van Wijngaarden T, Pols HA, Buurman CJ, van den Bemd GJ, Dorssers LC, Birkenhager JC, van Leeuwen JP (1994b) Inhibition of breast cancer cell growth by combined treatment with vitamin D3 analogues and tamoxifen. Cancer Res 54:5711–5717

    CAS  Google Scholar 

  • Wu G, Fan RS, Li W, Ko TC, Brattain MG (1997) Modulation of cell cycle control by vitamin D3 and its analogue, EB1089, in human breast cancer cells. Oncogene 15:1555–1563

    Article  PubMed  CAS  Google Scholar 

  • Xie SP, James SY, Colston KW (1997) Vitamin D derivatives inhibit the mitogenic effects of IGF-I on MCF-7 human breast cancer cells. J Endocrinol 154:495–504

    Article  PubMed  CAS  Google Scholar 

  • Yang W, Freedman LP (1999) 20-Epi-analogues of 1,25-dihydroxyvitamin D3 are highly potent inducers of DRIP coactivator complex binding to the vitamin D3 receptor. J Biol Chem 274:16838–16845

    Article  PubMed  CAS  Google Scholar 

  • Zhou JY, Norman AW, Chen DL, Sun GW, Uskokovic M, Koeffler HP (1990) 1,25-Dihydroxy-16-ene-23-yne-vitamin D3 prolongs survival time of leukemic mice. Proc Natl Acad Sci USA 87:3929–3932

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Hematology/Oncology Cedars Sinai Medical Center, UCLA School of Medicine, 8700 Beverly Boulevard, Los Angeles, CA, 90048, USA

    James O’Kelly

Authors
  1. James O’Kelly
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. Phillip Koeffler
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Hautklinik und Poliklinik der Universitätskliniken des Saarlandes, Kirrberger Str., 66421, Homburg/Saar

    Jörg Reichrath  & Wolfgang Tilgen  & 

  2. Frauenklinik des Universitätsklinikums der Eberhard-Karls-Universität, Calwerstr. 7, 71076, Tübingen

    Michael Friedrich

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

O’Kelly, J., Koeffler, H.P. (2003). Vitamin D Analogs and Breast Cancer. In: Reichrath, J., Tilgen, W., Friedrich, M. (eds) Vitamin D Analogs in Cancer Prevention and Therapy. Recent Results in Cancer Research, vol 164. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-55580-0_23

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-55580-0_23

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-62435-3

  • Online ISBN: 978-3-642-55580-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation