Elsevier

Biochemical Pharmacology

Volume 44, Issue 12, 15 December 1992, Pages 2273-2280
Biochemical Pharmacology

Research paper
EB1089: A new vitamin D analogue that inhibits the growth of breast cancer cells in vivo and in vitro

https://doi.org/10.1016/0006-2952(92)90669-AGet rights and content

Abstract

EB1089 is a novel vitamin D analogue which has been tested for its effects on breast cancer cell growth in vitro, using the established human breast cancer cell line MCF-7, and in vivo on the growth of established rat mammary tumours. Both EB1089 and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) inhibited MCF-7 cell proliferation with the synthetic analogue being at least an order of magnitude more potent than the native hormone. In vivo anti-tumour effects were investigated using the N-methyl-nitrosourea-induced rat mammary tumour model. Oral treatment with EB1089 was tested at three doses. With the lower dose, significant inhibition of tumour growth was seen in the absence of a rise in serum calcium. The same dose of 1,25-(OH)2D3 had no effect on tumour growth but caused hypercalcaemia. With the higher dose of EB1089, striking tumour regression was seen although serum calcium rose. This report demonstrates that EB1089 possesses enhanced anti-tumour activity coupled with reduced calcaemic effects relative to 1,25-(OH)2D3 and thus may have therapeutic potential as an anti-tumour agent.

References (43)

  • L. Binderup et al.

    20-Epi-vitamin D3 analogues: a novel class of potent regulators of cell growth and immune responses

    Biochem Pharmacol

    (1991)
  • M.R. Haussler et al.

    Molecular biology of the vitamin D hormone

    Recent Prog Hormone Res

    (1988)
  • J.W. Pike et al.

    Chicken intestinal receptor for 1,25-dihydroxyvitamin D3. Immunologic characterization and homogeneous isolation of a 60,000-dalton protein

    J Biol Chem

    (1987)
  • H. Reichel et al.

    The role of the vitamin D endocrine system in health and disease

    N Engl J Med

    (1989)
  • E. Abe et al.

    Differentiation of mouse myeloid leukemia cells induced by 1,25-dihydroxyvitamin D3

  • D. Bar-Shavitz et al.

    Induction of monocytic differentiation and bone resorption by 1,25-dihydroxyvitamin D3

  • W. Rigby et al.

    Differentiation of a human monocytic cell line by 1,25 dihydroxyvitamin D3 (calcitriol). A morphologic phenotype and functional analysis

    Blood

    (1983)
  • K.W. Colston et al.

    1,25-dihydroxyvitamin D3 and malignant melanoma: the presence of receptors and inhibition of growth in culture

    Endocrinology

    (1981)
  • R.J. Frampton et al.

    Inhibition of human cancer cell growth by 1,25-dihydroxyvitamin D3 metabolites

    Cancer Res

    (1983)
  • J. Hosomi et al.

    Regulation of terminal differentiation of cultured mouse epidermal cells by 1α,25-dihydroxyvitamin D3

    Endocrinology

    (1983)
  • M. Koga et al.

    Regulation of epidermal growth factor receptor levels by 1,25-dihydroxyvitamin D3 in human breast cancer cells

    Cancer Res

    (1988)
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