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

A. De Cupis, D. Noonan, P. Pirani, A. Ferrera, L. Clerico, R. E. Favoni

Research output: Contribution to journalArticlepeer-review

Abstract

1. This study has two specific aims: (a) to compare the antioestrogenic activity of two steroidal analogues of 17β-oestradiol, the 7α-alkylamide, ICI 164,384 and the 7α-alkylsulphinylamide, ICI 182,780, with that of the triphenylethylene-derived compound 40H-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 ICE-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 K(D), B(max) and sites/cell. 3. Our results indicate that ICI 182,780 and ICI 164,384 are 1.5-5.5 fold more potent than 40H-tamoxifen in inhibiting the basal proliferation of oestrogen-receptor positive (ER+) breast cancer cell lines. Moreover we demonstrate the capacity of ICI 182,780 and ICI 164,384 to reduce, in a time-dependent fashion, oestrogen- and/or IGF-I-stimulated growth of ER+ cell lines, possibly by negatively interfering with an IGF-I-like material secretion and IGF-I-receptor number. 4. Our data provide the first evidence that, on ER+ human breast carcinoma cell lines, steroidal antioestrogens inhibit cell growth and modulate the IGF-I mitogenic system. The mechanism of this latter effect has yet to be identified.

Original languageEnglish
Pages (from-to)2391-2400
Number of pages10
JournalBritish Journal of Pharmacology
Volume116
Issue number5
Publication statusPublished - 1995

Keywords

  • Antioestrogens
  • Growth factors
  • Human breast cancer
  • Oestrogens

ASJC Scopus subject areas

  • Pharmacology

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