Anti-proliferative and anti-estrogenic effects of ICI 164,384 and ICI 182,780 in 4-OH-tamoxifen-resistant human breast-cancer cells

Int J Cancer. 1994 Jan 15;56(2):295-300. doi: 10.1002/ijc.2910560225.

Abstract

The effects of the anti-estrogens 4-hydroxytamoxifen (OHTam), ICI 164,384 and ICI 182,780 were tested on the MCF-7/LCC2 breast-carcinoma cell line, which grows significantly in the presence of OHTam and serves as a model for studying anti-estrogen resistance of estrogen-receptor-positive breast cancer. Cell proliferation and cathepsin-D secretion were strongly inhibited by either ICI 182,780 or ICI 164,384 alone or ICI 164,384 in combination with 17-beta-estradiol (E2) or OHTam. ICI 164,384 alone did not affect the cathepsin-D and pS2 mRNA levels, but antagonized the stimulatory effects of E2 or OHTam on these 2 mRNAs. OHTam was more effective than E2 in increasing cathepsin-D mRNA levels, supporting the idea that anti-estrogen-resistant breast cancer continues to overexpress cathepsin-D. These data show that the steroidal anti-estrogens ICI 164,384 and ICI 182,780 retain their ability to inhibit cell proliferation and the estrogen-responsiveness of cathepsin-D and pS2 genes in the OHTam-resistant MCF-7/LCC2 cell lines. These pure anti-estrogens may thus be efficient second-line treatments of some Tamoxifen-resistant tumors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / ultrastructure
  • Cathepsin D / genetics
  • Cell Division / drug effects
  • Drug Resistance
  • Estradiol / analogs & derivatives*
  • Estradiol / pharmacology
  • Estrogen Antagonists / pharmacology*
  • Estrogens / pharmacology
  • Estrogens / physiology
  • Fulvestrant
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Neoplasm Proteins / genetics
  • Neoplasms, Hormone-Dependent / drug therapy*
  • Neoplasms, Hormone-Dependent / pathology
  • Neoplasms, Hormone-Dependent / ultrastructure
  • Polyunsaturated Alkamides
  • Proteins*
  • Receptors, Estrogen / physiology
  • Tamoxifen / analogs & derivatives*
  • Tamoxifen / antagonists & inhibitors
  • Tamoxifen / pharmacology
  • Trefoil Factor-1
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins

Substances

  • Antineoplastic Agents
  • Estrogen Antagonists
  • Estrogens
  • Neoplasm Proteins
  • Polyunsaturated Alkamides
  • Proteins
  • Receptors, Estrogen
  • TFF1 protein, human
  • Trefoil Factor-1
  • Tumor Suppressor Proteins
  • Tamoxifen
  • afimoxifene
  • Fulvestrant
  • Estradiol
  • ICI 164384
  • Cathepsin D