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Length increase of the side chain of idoxifene does not improve its antagonistic potency in breast-cancer cell lines

Lookup NU author(s): Dr Ian HardcastleORCiD

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Abstract

Linkage of specific residues onto steroidal estrogens through a long aliphatic side chain leads to “pure antiestrogens” devoid of residual estrogenic activity. Therefore, we assessed whether an increase in the length of the side chain of the triphenylethylenic antiestrogen idoxifene might increase its antagonistic potency. Culture of MCF-7 and tamoxifen-resistant variant RTX6 cells in the presence of CB 7675, a (CH₂)₈ derivative of idoxifene [(CH₂)₂], ruled out this possibility. This compound partly blocked MCF-7 cell growth only at 10⁻⁶ M to almost the same extent as tamoxifen and failed to inhibit the growth of RTX6 cells, whereas the pure antiestrogen RU 58 668 was effective on both cell lines at much lower concentration. This absence of improvement was reflected in the observation of an efficiency for down-regulating progesterone receptor no better than that of tamoxifen. Pure antiestrogens are known to down-regulate the estrogen receptor, whereas triphenylethylenic antiestrogens up-regulate the receptor; CB 7675 behaves as the latter in agreement with its lack of strong antagonistic activity.

Publication metadata

Author(s): Jin L, Legros N, LeClerq G, Hardcastle IR, Jarman M

Publication type: Article

Publication status: Published

Journal: Cancer Chemotherapy and Pharmacology

Year: 1998

Volume: 41

Issue: 4

Pages: 339-342

Print publication date: 28/01/1998

ISSN (print): 0344-5704

ISSN (electronic): 1432-0843

Publisher: Springer

URL: http://dx.doi.org/10.1007/s002800050748

DOI: 10.1007/s002800050748

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