title: Effects of peripheral-type benzodiazepine receptor ligands on Ehrlich tumor cell proliferation.
abstract: Peripheral-type benzodiazepine receptors have been found throughout the body, and particularly, in high numbers, in neoplastic tissues such as the ovary, liver, colon, breast, prostate and brain cancer. Peripheral-type benzodiazepine receptor expression has been associated with tumor malignity, and its subcellular localization is important to define its function in tumor cells. We investigated the presence of peripheral-type benzodiazepine receptors in Ehrlich tumor cells, and the in vitro effects of peripheral-type benzodiazepine receptors ligands on tumor cell proliferation. Our results demonstrate the presence of peripheral-type benzodiazepine receptor in the nucleus of Ehrlich tumor cells (85.53+/-12.60%). They also show that diazepam and Ro5-4864 (peripheral-type benzodiazepine receptor agonists) but not clonazepam (a molecule with low affinity for the peripheral-type benzodiazepine receptor) decreased the percentage of tumor cells in G0-G1 phases and increased that of cells in S-G2-M phases. The effects of those agonists were prevented by PK11195 (a peripheral-type benzodiazepine receptor antagonist) that did not produce effects by itself. Altogether, these data suggest that the presence of peripheral-type benzodiazepine receptor within the nucleus of Ehrlich tumor cells is associated with tumor malignity and proliferation capacity.
authors.affiliation: Laboratory of Applied Pharmacology and Toxicology, School of Veterinary Medicine, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Mônica
authors.initials: M
authors.lastname: Sakai
authors.forename: Evelise Souza Monteiro
authors.initials: ES
authors.lastname: Fonseca
authors.forename: Silvia Catarina Salgado
authors.initials: SC
authors.lastname: Oloris
authors.forename: Patrícia
authors.initials: P
authors.lastname: Matsuzaki
authors.forename: Andréia Hanada
authors.initials: AH
authors.lastname: Otake
authors.forename: Kátia Ramos Moura
authors.initials: KR
authors.lastname: Leite
authors.forename: Cristina Oliveira
authors.initials: CO
authors.lastname: Massoco
authors.forename: Maria Lúcia Zaidan
authors.initials: ML
authors.lastname: Dagli
authors.forename: João
authors.initials: J
authors.lastname: Palermo-Neto
mesh_terms: D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002998:Clonazepam / Q000494:pharmacology; D005434:Flow Cytometry; D018757:GABA Modulators / Q000494:pharmacology; D007150:Immunohistochemistry; D007546:Isoquinolines / Q000494:pharmacology; D008024:Ligands; D051379:Mice; D011963:Receptors, GABA-A / Q000096:biosynthesis / Q000187:drug effects*
chemical_list: D001570:Benzodiazepinones; D018757:GABA Modulators; D007546:Isoquinolines; D008024:Ligands; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam; D002998:Clonazepam; C037850:PK 11195