Response of estrogen receptor containing tumour cells to pure antiestrogens and the calmodulin inhibitor, calmidzolium chloride

Christopher J. Newton, Katherine Eycott, Victoria Green, Stephen Atkin

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Cell survival is dependent on both external and internally generated signalling processes and current strategies for medical intervention in neoplastic disease are directed towards signal transduction blockade. Redundancy in signalling pathways may mean, however, that a combination of agents is required for the maximal therapeutic benefit. We have explored this idea with regard to the antiestrogen sensitivity of estrogen dependent tumours. Using estrogen receptor (ER) containing tumour cell lines, we have determined whether antiestrogens increase the cytotoxicity of the potent calmodulin inhibitior, calmidzolium chloride (CCl). For the pituitary tumour cell line GH3, CCl induces a form of apoptotic cell death and co-treatment with the pure antiestrogen, ZM 182780, enhances sensitivity to the calmodulin inhibitor, by at least two fold. In contrast to the pure steroidal antiestrogens, the triphenylethylenes, tamoxifen and 4-hydroxytamoxifen give no enhancing effect on CCl induced cell death. Although CCl induces apoptosis of several ER containing breast cancer cell lines, unlike the pituitary tumour cells, ZM 182780 is unable to increase their sensitivity to calmodulin inhibition. Further studies strongly suggest that cell death in response to calmodulin inhibition is the result of metabolic disruption and that for GH3 cells, this is enhanced by antiestrogen treatment. Copyright (C) 2000 Elsevier Science Ltd.

Original languageEnglish
Pages (from-to)29-38
Number of pages10
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume73
Issue number1-2
DOIs
Publication statusPublished - 1 May 2000
Externally publishedYes

Fingerprint

Estrogen Receptor Modulators
Calmodulin
Estrogen Receptors
Chlorides
Tumors
Cells
Cell death
Cell Death
Pituitary Neoplasms
Neoplasms
Tumor Cell Line
Signal transduction
Tamoxifen
Cytotoxicity
Redundancy
Signal Transduction
Cell Survival
Estrogens
Apoptosis
Breast Neoplasms

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this

Response of estrogen receptor containing tumour cells to pure antiestrogens and the calmodulin inhibitor, calmidzolium chloride. / Newton, Christopher J.; Eycott, Katherine; Green, Victoria; Atkin, Stephen.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 73, No. 1-2, 01.05.2000, p. 29-38.

Research output: Contribution to journalArticle

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