Peripheral-type benzodiazepine receptors in the regulation of proliferation of MCF-7 human breast carcinoma cell line

Iris Carmel, Fuad A. Fares, Svetlana Leschiner, Hans Scherübl, Gary Weisinger, Moshe Gavish

Research output: Contribution to journalArticlepeer-review

Abstract

Peripheral-type benzodiazepine receptors (PBR) have been implicated in cell proliferation. The aim of the present study was to test the effect of the PBR ligands PK 11195 and Ro 5-4864 and the central-type benzodiazepine receptor ligand clonazepam on breast carcinoma cell proliferation, using [3H] thymidine incorporation. We then carried out a study to identify where the PBR-specific ligands Ro 5-4864 and PK 11195 act in the cell cycle, using flow cytometric analysis. We found PBR expression in the malignant breast cancer tumors, representing various levels of estrogen and/or progesterone receptors, as well as in the MCF-7 breast carcinoma cell line. PK 11195 and Ro 5-4864 inhibited cell proliferation at concentrations of 10-5 to 10-4 M, while clonazepam (the central-type benzodiazepine receptor-specific ligand) had no effect. In this same concentration range, PK 11195 and Ro 5-4864, in contrast to clonazepam, induced an accumulation of MCF-7 cells in both the G0-G1 and G2-M phases of the cell cycle. The present study demonstrates that PBR ligands play a role in regulating cell proliferation in the human breast carcinoma cell line MCF-7. Copyright (C) 1999 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)273-278
Number of pages6
JournalBiochemical Pharmacology
Volume58
Issue number2
DOIs
StatePublished - 15 Jul 1999
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by grants (to S.L. and G.W.) from the Center for Absorption in Science and the Ministry of Immigrant Absorption of the State of Israel, as well as by Grant 181-922 (to M.G.) from the Fund for Research Promotion at the Technion. We thank Ruth Singer for editing the manuscript.

Keywords

  • Cell cycle
  • Cell proliferation
  • MCF-7
  • PK 11195
  • Peripheral-type benzodiazepine receptor
  • Ro 5-4864

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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