Here's a recent paper showing that EB 1089 (Vitamin D derivative) and Panretin (9-cis retinoic acid) produce additive effects when used to treat human breast cancer cells (MCF-7):
J Endocrinol 1997 Sep;154(3):495-504
Vitamin D derivatives inhibit the mitogenic effects of IGF-I
on MCF-7 human breast cancer cells.
Xie SP, James SY, Colston KW
Division of Gastroenterology, Endocrinology and Metabolism, St George's Hospital Medical
School, London, UK.
The effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and four novel synthetic analogues
(EB1089, KH1060, KH1230 and CB1093) on IGF-I-stimulated growth of MCF-7 human breast
cancer cells have been determined. A significant time- and dose-dependent inhibition of
IGF-I-stimulated cell growth was seen with EB1089, such that after 7 days of treatment with 10(-8)
M EB1089, the mitogenic effect of IGF-I (30 ng/ml) was negated. Comparison with 1,25(OH)2D3
showed the synthetic analogues to be more potent. The anti-oestrogen ICI 182,780 similarly
inhibited IGF-I-stimulated growth of these cells and in combination with EB1089 exerted additional
inhibitory effects. Retinoids (all-trans-retinoic acid or the isomer 9-cis-retinoic acid) were less
effective in limiting MCF-7 cell responsiveness to IGF-I but, in combination with EB1089, a
co-operative effect was achieved. Using radioligand-binding techniques, we observed that
1,25(OH)2D3 and EB1089 down-regulated the levels of 125I-IGF-I binding to MCF-7 cell
membranes. Scatchard analysis showed that EB1089 decreased maximal binding approximately
2-fold. Vitamin D derivatives were also demonstrated to reduce IGF-I receptor expression in
MCF-7 cells by Western analysis. Our findings demonstrate that vitamin D derivatives limit
responsiveness of MCF-7 cells to the mitogenic effects of IGF-I, which may be mediated by
reduction of IGF-I receptor expression.
PMID: 9379127, UI: 98022033 |
