Peripheral-type benzodiazepine receptors in the regulation of proliferation of MCF-7 human breast carcinoma cell line.
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.
Carmel
I
I
Department of Pharmacology, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa.
Fares
F A
FA
Leschiner
S
S
Scherübl
H
H
Weisinger
G
G
Gavish
M
M
D000970:Antineoplastic Agents / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D058785:GABA-A Receptor Agonists; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D008024:Ligands; D011963:Receptors, GABA-A / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001570:Benzodiazepinones; D058785:GABA-A Receptor Agonists; D007546:Isoquinolines; D008024:Ligands; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam; D004247:DNA; C037850:PK 11195