Comparison between novel steroid-like and conventional nonsteroidal antioestrogens in inhibiting oestradiol- and IGF-I-induced proliferation of human breast cancer-derived cells

British Journal of Pharmacology
A De CupisR E Favoni

Abstract

1. This study has two specific aims: (a) to compare the antioestrogenic activity of two steroidal analogues of 17 beta-oestradiol, the 7 alpha-alkylamide, ICI 164,384 and the 7 alpha-alkylsulphinylamide, ICI 182,780, with that of the triphenylethylene-derived compound 4OH-tamoxifen on a pool of human breast cancer cell lines (HBCCL) with a range of hormonal responsiveness and acquired anti-oestrogen resistance and (b) to investigate the ability of such antioestrogens to modulate the potent breast carcinoma growth-stimulatory activity of the 'IGF-I system'. 2. For the chemosensitivity investigations we used a long-term colorimetric and the short-term thymidine incorporation assay; we analysed IGF-I in conditioned media by a radioimmunoassay, IGF-I mRNA in the cells by RT-PCR and molecular species of IGF-I-binding proteins, secreted in conditioned media, by Western ligand blot. IGF-I receptors were assayed on cell monolayers by binding studies and by Scatchard analysis, we calculated KD, Bmax and sites/cell. 3. Our results indicate that ICI 182,780 and ICI 164,384 are 1.5-5.5 fold more potent than 4OH-tamoxifen in inhibiting the basal proliferation of oestrogen-receptor positive (ER+) breast cancer cell lines. Moreover we demonst...Continue Reading

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Citations

Apr 12, 2002·International Journal of Cancer. Journal International Du Cancer·Marcello VendittiRobert P C Shiu
Aug 2, 2003·European Journal of Pharmacology·Alessandra de CupisRoberto E Favoni
Jul 1, 1997·Trends in Pharmacological Sciences·A de Cupis, R E Favoni
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May 5, 2011·Endocrinology·Timothy E RichardsonJames W Simpkins
Oct 3, 2012·American Journal of Reproductive Immunology : AJRI·Danica K HickeyCharles R Wira
Jan 13, 2011·American Journal of Reproductive Immunology : AJRI·John V FaheyCharles R Wira
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Mar 5, 1999·Breast Cancer Research and Treatment·M J EllisA Harris
Apr 3, 1999·International Journal of Cancer. Journal International Du Cancer·M SalernoE Surmacz

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